Liquid and plate sensors for microplate injector system

ABSTRACT

In a sample analyzing apparatus, an injector assembly injects a reagent onto a sample, and luminescent light from the sample is transmitted to a detector. The assembly may be movable toward and away from the sample. The assembly may include one or more needles that communicate with one or more reservoirs supplying reagent or other liquids. The assembly may include a light guide for communicating with the detector. A cartridge may be provided in which the assembly, one or more reservoirs, and one or more pumps are disposed. The cartridge and/or the apparatus may be configured for enabling rinsing or priming to be done outside the apparatus. The cartridge and/or the apparatus may include one or more types of sensors configured for detecting, for example, the presence of liquid or bubbles in one or more locations of the apparatus and/or the cartridge.

TECHNICAL FIELD

This present invention generally relates to analytical instruments,including multimode analytical instruments and cartridges utilized withsuch instruments, and methods related to such instruments andcartridges. In particular, the invention relates to measuringluminescent emissions from samples utilizing such instruments,cartridges and methods, and to addressing problems associated with theuse of reagents and other liquids in conjunction with luminescencemeasurement.

BACKGROUND

Various analytical instruments have been developed for makingoptics-based measurements (e.g., fluorescence, luminescence, andabsorbance) as part of assays useful in the life science industry. Manyanalytical instruments are designed to carry out only one or a fewdedicated types of measurements. On the other hand, multimode analyticalinstruments, also referred to as multimode readers, are designed toperform multiple analytical assays in a single instrument. Multimodeanalytical instruments may be designed to be re-configurable to enable auser to select different types of measurements to be performed. Somemultimode analytical instruments utilize application-specific cartridgesto enable re-configuration. Examples of multimode analytical instrumentsare described in U.S. Patent Application Nos. 2005/0012929;2005/0105080; and 2003/0048447, for example. Additional examples includeU.S. Pat. No. 8,119,066, and U.S. Patent Application Pub. No.2012/0077282.

In the case of performing flash luminescence, a reagent must be injectedonto the sample to induce the luminescent response. In the case ofmultimode readers that utilize cartridges, there is a need forintegrating the reagent injection function and the luminescence readingfunction into a single cartridge. Moreover, because luminescenceexperiments require a fluidic system to dispense reagent liquid, such asystem must be periodically rinsed and primed, and possibly cleaned ordecontaminated. Hence, luminescence experiments may entail a variety ofdifferent types of liquid flows, which may lead to undesiredcontamination of optics components of the sample analyzing apparatus andother problems. As examples, contamination may result fromelectrostatically accelerated droplets, the generation of uncontrolleddroplet sizes, the unwanted dispensing or spilling of liquid ontosensitive optics components, and the development of leaks in the fluidicsystem. Therefore, there is also a need for sample analyzingapparatuses, including those utilizing luminescence cartridges, whichaddress such problems.

SUMMARY

To address the foregoing problems, in whole or in part, and/or otherproblems that may have been observed by persons skilled in the art, thepresent disclosure provides methods, processes, systems, apparatus,instruments, and/or devices, as described by way of example inimplementations set forth below.

According to one embodiment, a sample analyzing apparatus includes: anapparatus housing; a sample carrier disposed in the apparatus housingand configured for supporting a sample; a reagent reservoir; a pumpcommunicating with the reagent reservoir; an injector assembly disposedin the apparatus housing and comprising an injector housing and aninjector needle extending through the injector housing and configuredfor communicating with the reagent reservoir via the pump; and aluminescence detector positioned in the apparatus housing to receiveoptical signals from the sample.

According to another embodiment, the sample analyzing apparatus includesa luminescence cartridge removably mounted at the sample analyzingapparatus, the luminescence cartridge comprising a cartridge housingcomprising a cartridge housing opening, and a driver disposed in thecartridge housing, wherein the reservoir support and the pump aredisposed in the cartridge housing, and the injector assembly is at leastpartially disposed in the cartridge housing and is movable by the driverthrough the cartridge housing opening and alternately toward and awayfrom the sample carrier.

According to another embodiment, a luminescence cartridge for use in asample analyzing apparatus includes: a cartridge housing comprising acartridge housing opening; a reservoir support disposed in the cartridgehousing and configured for supporting a reagent reservoir; a pumpcommunicating with the reagent reservoir; a driver disposed in thecartridge housing; an injector/reader assembly at least partiallydisposed in the cartridge housing and comprising an injector/readerhousing, an injector needle extending through the injector/readerhousing and configured for communicating with a reagent reservoirsupported by the reservoir support via the pump, and a light guideextending through the injector/reader housing and configured forcommunicating with a luminescence detector, wherein the injector/readerassembly is movable by the driver through the cartridge housing openingand alternately toward and away from the cartridge housing; and anelectrical connector mounted at the cartridge housing and in signalcommunication with the driver and the pump, the electrical connectorconfigured for removable coupling to the sample analyzing apparatus toreceive power from and transmit signals to or from the sample analyzingapparatus.

According to another embodiment, a sample analyzing apparatus includes:a luminescence cartridge according to any of the embodiments disclosedherein; an apparatus housing; a sample carrier disposed in the apparatushousing; and a cartridge support configured for receiving theluminescence cartridge such that the luminescence cartridge is removablymounted thereto, the cartridge support movable between an insidecartridge support position at which the cartridge support is positionedentirely in the apparatus housing and an outside cartridge supportposition at which the cartridge support is positioned at least partiallyoutside the apparatus housing, wherein: the injector/reader assembly ismovable by the driver alternately toward and away from the samplecarrier; and at least one of the sample carrier and the cartridgesupport is movable to align the injector/reader assembly with a samplecontained on the sample carrier.

According to another embodiment, a method for analyzing a sampleincludes: positioning an injector assembly in alignment with and at adesired distance from a sample in a sample analyzing apparatus, theinjector assembly comprising an injector housing and an injector needleextending through the injector housing; injecting a reagent from theinjector needle to the sample by operating the pump to establish a flowof the reagent from a reagent reservoir to the injector needle; anddetecting luminescent light emitted from the sample at a luminescencedetector.

According to another embodiment, the sample analyzing apparatuscomprises a cartridge support, and the method further includes: loadinga luminescence cartridge on the cartridge support, wherein theluminescence cartridge comprises a cartridge housing comprising acartridge housing opening, the pump and the reagent reservoir aredisposed in the cartridge housing, and the injector assembly is at leastpartially disposed in the cartridge housing and extends through thecartridge housing opening; and before aligning the injector assemblywith the sample, moving the luminescence cartridge into an apparatushousing of the apparatus by operating the cartridge support.

Other devices, apparatus, systems, methods, features and advantages ofthe invention will be or will become apparent to one with skill in theart upon examination of the following figures and detailed description.It is intended that all such additional systems, methods, features andadvantages be included within this description, be within the scope ofthe invention, and be protected by the accompanying claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be better understood by referring to the followingfigures. The components in the figures are not necessarily to scale,emphasis instead being placed upon illustrating the principles of theinvention. In the figures, like reference numerals designatecorresponding parts throughout the different views.

FIG. 1A is a schematic view of an example of components of a cartridgeaccording to some embodiments.

FIG. 1B is a schematic view of an example of components of a cartridgeused for a fluorescence application according to some embodiments.

FIG. 1C is a schematic view of an example of components of a cartridgeused for an absorbance application according to some embodiments.

FIG. 2 is a schematic view of an example of a luminescence cartridge,having an integrated read head, according to some embodiments.

FIG. 3 is a schematic view of an example of a luminescence cartridge,having an integrated detector, according to some embodiments.

FIG. 4 is a schematic top view of an example of a cartridge systemaccording to some embodiments.

FIG. 5 is a schematic view of an example of a top and bottom readingcartridge system according to some embodiments.

FIG. 6 is a schematic top view of the cartridge configuration shown inFIG. 5.

FIG. 7 is a schematic view of an example of a flash fluorescencecartridge system according to some embodiments.

FIG. 8 is a schematic top view of an example of a flash luminescencecartridge system according to some embodiments.

FIG. 9A is a schematic top view of an example of a sample analyzingsystem or apparatus according to some embodiments.

FIG. 9B is a schematic side view of the sample analyzing system orapparatus illustrated in FIG. 9A.

FIG. 10 is a schematic view of an example of a sample analyzing systemor apparatus according to some embodiments.

FIG. 11 is a perspective view of an example of an injector orinjector/reader assembly according to some embodiments.

FIG. 12A is a perspective view of the tip (distal) section of theinjector or injector/reader assembly illustrated in FIG. 11 whensurfaces are clean and no bubbles are being generated.

FIG. 12B is a perspective view of the tip (distal) section of theinjector or injector/reader assembly illustrated in FIGS. 11 and 12Awhen bubbles have been generated in an associated injector system as aresult of dispensing a liquid/air mixture.

FIG. 13A is a top schematic view of the sample analyzing apparatusillustrated in FIG. 10 in which a cartridge support and a luminescencecartridge loaded thereon are in an inside position, i.e., fully insidean apparatus housing.

FIG. 13B is a top schematic view of the sample analyzing apparatusillustrated in FIGS. 10 and 13A in which the cartridge support and theluminescence cartridge loaded thereon are have been moved to an outsideposition, i.e., extending at least partially outside of the interior ofthe apparatus housing.

FIG. 14 is a perspective view of an example of the externalrinsing/priming station according to some embodiments.

FIG. 15 is a perspective view of the external rinsing/priming stationillustrated in FIG. 14 as mounted to a cartridge support and/or aluminescence cartridge.

FIG. 16 is a schematic view of an example of a capacitive bubble sensorin operative communication with an injector needle and associated fluidline (shown in cross-section) according to some embodiments.

FIG. 17 is a schematic cross-sectional view of an injector orinjector/reader assembly and electronics of a luminescence cartridgeaccording to some embodiments.

FIG. 18 is an elevation view of the sample analyzing apparatusillustrated in FIG. 10 in which a gap sensor is provided in theapparatus housing below a luminescence cartridge.

FIG. 19 is an elevation view of a luminescence cartridge in which aliquid sensor is provided in a cartridge housing according to someembodiments.

FIG. 20 is a schematic cross-sectional view of another example of aninjector or injector/reader assembly and electronics of a luminescencecartridge, according to an embodiment.

DETAILED DESCRIPTION

According to embodiments disclosed herein, a sample analyzing apparatusis provided in which an injector assembly injects a reagent onto asample. The sample emits luminescent light in response to the reagent,which is transmitted to a detector. In some embodiments, the injectorassembly is movable toward and away from the sample, which may be donein an automated manner using a driver. The injector assembly may includeone or more needles that communicate with one or more reservoirssupplying reagent or other liquids. In some embodiments, the injectorassembly further includes a light guide for communicating with thedetector. In some embodiments, a cartridge may be provided in which theinjector assembly, one or more reservoirs, and one or more pumps aredisposed. The cartridge and/or the sample analyzing apparatus may beconfigured for enabling rinsing or priming to be done outside theapparatus. The cartridge and/or the apparatus sample analyzing mayinclude one or more types of sensors configured for detecting, forexample, the presence of liquid or bubbles in one or more locations ofthe sample analyzing apparatus and/or the cartridge.

Referring now to FIGS. 1A, 1B, and 1C a cartridge 10 for use in anapparatus 12 for analyzing a target 14 in a sample 16 is shown. Thesample 16 may be held within the apparatus 12 on a sample support 17,such as a microplate. As shown in FIG. 1, the cartridge 10 comprises oneor more light sources 18 that separately or in combination produce anexciting light 20. The cartridge 10 is designed to be removably engagedwith the apparatus 12. The cartridge 10 has a first optical system 22which has components for directing the exciting light 20 to the sample16. The light source 18, such as a light emitting diode (LED) or a laserdiode (LD), is collimated by lenses and apertures to emit a collimatedbeam of light. The first optical system 22 then transmits the excitinglight 20 through filters 24, such as a bandpass filter, and thenreflects the exciting light 20 out of the cartridge 10 with the help ofa reflector 26, such as a dichroic beamsplitter, to a read head 28. Theread head 28 directs the exciting light 20 toward the sample 16. Theread head 28 contains an objective lens 30 that can be moved up anddown. The objective lens 30 focuses the exciting light 20 onto thesample 16. The sample 16, containing the target 14, then produces anemitting light 32 (or emitted light 32), which is directed to an opticaloutput detector 36, having a photomultiplier tube (PMT) 96, as shown inFIG. 1B, or a photodiode 38, as shown in FIG. 1C.

As also shown in FIGS. 1B and 1C the apparatus 12 is part of a systemfor analyzing a sample. The system comprises a structure 50, alsoreferred to herein as a housing or apparatus housing, which is engaged(i.e., attached) to the read head 28, the detector 36, a power source44, and a movable cartridge support 52. The movable cartridge support 52positions the cartridge 10 within the apparatus 12 and is capable ofsupporting a plurality of cartridges and aligning each cartridge withthe read head 28 and the detector 36. The cartridge 10 has a coupler 46for providing a current supply from the power source 44 to the lightsource 18. In some embodiments, the cartridge 10 is mounted onto thesupport 52 and a plug terminating the electronics inside of thecartridge 10 is connected with a socket in the support 52. At thesocket, several low voltage output lines of the power source 44 areavailable and interface lines with the main apparatus controller. Thecoupler 46 functions in connecting the cartridge 10 with othercomponents in the apparatus 12, such as for receiving low DC voltage forthe cartridge light source 18 and other electronics; establishingcontrol lines for LED current adjustment; establishing control lines forcartridge recognition; data lines (e.g., an electronic bus) fordetectors within the cartridge 10 (e.g., a photodiode for sendingmeasured data to a controller); and synchronization lines forsynchronizing pulses of the light source 18 with the data acquisitionfrom detector(s) and other circuitry within the apparatus 12, such asphoton counting circuitry in the main apparatus controller. In someembodiments, the coupler 46 is made from two parts, a printed circuitboard that extends along the cartridge support 52, providing a socketfor one or more cartridges 10, and a flexible flat cable at the end,bridging the gap to the main apparatus controller (flexible, because thecartridge support 52 can be moved). The electronic bus, or data linefunction is designed as of the type SPI (serial peripheral interface).

The system may also have a sample support carrier (or sample carrier)54, such as a microplate scanning stage, attached to the structure formoving the sample support 17 either horizontally or vertically withinthe apparatus housing (e.g., structure 50).

Referring now to FIG. 1B, in certain embodiments, such as a cartridge 10that is used for a fluorescence application, the emitting light 32 iscollected from the target 14 by the read head 28 and collimated backinto the cartridge 10. The cartridge 10 has a second optical system 34,which receives the emitted light 32 from the read head 28 and directsthe emitted light 32 from the sample 16 to the detector 36. The emittinglight 32 received from the read head 28 is transmitted through thereflector 26, and is then directed with a reflector 48 towards thecartridge exit 40, which interfaces with the detector 36 via a detectorport 49. Before exiting the cartridge 10, the emitted light 32 isfiltered through a filter 42, such as a bandpass filter, to rejectcontributions of excitation light being scattered back from the readhead 28 and the sample 16. The entire path after the emitted light 32has passed through the reflector 26 is optically shielded from thoseareas of the cartridge 10 which may be floated with diffuse scatter ofexciting light 20.

Referring now to FIG. 1C, in certain embodiments, a cartridge 10, suchas a cartridge that is used for an absorbance application, is positionedin the apparatus 12 in opposite to the detector 36. According to thisembodiment, the exciting light 20 is transmitted through the sample 16and sample support carrier 54 via an aperture 56 (i.e., a window orlight transparent portion) in the sample support carrier 54 and anaperture 58 (i.e., a window or light transparent portion) in the samplesupport 17. Emitting light 32 from the target 14 is directed to thedetector 36 (containing, e.g., a photodiode 38). The configuration ofthe cartridge 10 for measuring absorbance as shown in FIG. 1C is shownby way of example and other configurations are possible, for example,the cartridge 10 may be alternately positioned within the apparatus 12,such as in the same approximate plane as the detector 36 (e.g.,side-by-side), and the emitting light 32 may be relayed to the detector36, such as with a light guide, as will be understood by those of skillin the art with reference to this disclosure. In some embodiments, theabsorbance cartridge 10 may be a dual wavelength absorbance cartridge ora wide band light source absorbance cartridge as further described inabove-referenced U.S. Pat. No. 8,119,066.

The one or more light sources 18 housed in the cartridge 10 may beselected from suitable light sources known to those of skill in the artsuch as light emitting diodes (LEDs), laserdiodes, and a Xenon flashlamp module. In some embodiments, when the cartridge 10 is used for afluorescence application, such as shown in FIG. 1B, the light source 18is one or more LED light sources.

Referring now to FIG. 2, a luminescence cartridge 200 for use in anapparatus 12 for analyzing a target 14 in a sample 16 is shown. As shownin FIG. 2, the cartridge 200 comprises an integrated read head 202 and adriver 204, which moves the read head 202 in the direction indicated byarrow 205 into a detection position above the sample 16 when receivingemitting luminescent light 206 from the sample 16. The integrated readhead 202 can also be moved by the driver 204 away from the sample 16into a latent position when the luminescence cartridge 200 is not inuse, or the apparatus 12 is being loaded with a new sample support 17.In some embodiments, the read head 202 is fully retractable into thecartridge 200. In some embodiments, for reasons of saving measurementtime, the read head 202 will not move up and down when moving from theone sample 16 to the next, but will stay in proximity above the samplesupport 17, when moving from one sample 16 to the next sample. Theintegrated read head 202 is retracted when the sample support 17 ismoved in or out of the apparatus 12 in order to avoid parts of thesample support carrier (not shown) that extend beyond the upper samplesupport level.

In some embodiments, the integrated read head 202 is a rigid light guidethat receives emitting luminescent light 206 at a distal end 208 of theintegrated read head 202 from a position above the sample holder 17 andsample 16. The emitting luminescent light 206 then exits the integratedread head 202 at a proximal end 210 of the integrated read head 202 andis collimated by a lens 212 to produce a collimated light beam 218.

According to an embodiment of the luminescence cartridge 200 shown inFIG. 2, the apparatus 12 and luminescence cartridge 200 may beconfigured for a bioluminescence resonance energy transfer (BRET) typemeasurement, where luminescence light is composed of two wavelengthbands (e.g., a dual emission cartridge configuration) and which may bedetected simultaneously with a dual channel detector. Examples of a dualemission cartridge and dual channel detector are further described inabove-referenced U.S. Pat. No. 8,119,066. As shown in FIG. 2, thecollimated emitting luminescent light beam 218 is redirected with areflector 214 toward a dichroic beamsplitter 88 via a lens 216 andseparated into two wavelength bands 218 a and 218 b. The firstwavelength band 218 a is passed or transmitted by a beamsplitter 88toward the detector 36 via a first emission filter 90 (e.g., a bandpassfilter). The second wavelength band 218 b is reflected by thebeamsplitter 88, and reflected at the mirror 92 toward the detector 36via a second emission filter 94 (e.g., a bandpass filter). In someembodiments, the detector 36 is a dual channel detector having twodetectors 96 and 98 (e.g., photomultiplier tubes) stacked to form thedual channel detector. In addition, the luminescence cartridge 200 has adual exit port 100 and 102, which is aligned with the detectors 96 and98 via detector ports 104 and 106.

In an alternative embodiment, for a wider class of luminescencemeasurements, which do not require simultaneous measurement of twowavelength bands, the cartridge 200 may be simplified by omitting thebeamsplitter 88, mirror 92, and second emission filter 94.

FIG. 3 is a schematic view of an example of a luminescence cartridge 300according to another embodiment. The luminescence cartridge 300 may beutilized in conjunction with the apparatus 12 as a system for analyzinga target 14 in a sample 16. Like the cartridges described above andillustrated in FIGS. 1A-2, the luminescence cartridge 300 is designed tobe removably engaged with the apparatus 12 by loading (mounting,installing) the luminescence cartridge 300 on the cartridge support 52,and may be replaced or exchanged with other cartridges of the same ofdifferent type.

The luminescence cartridge 300 includes a cartridge housing 304 that issized and configured to be removably loaded or mounted on the cartridgesupport 52. The luminescence cartridge 300 also includes an integratedluminescence detector 308 that is movable through an opening 220 of thecartridge housing 304. In typical embodiments, the luminescence detector308 is linearly movable in a reciprocating manner as indicated by anarrow 205, i.e., alternately toward the cartridge housing 304 (and thusaway from the sample carrier 54) to selected retracted positions andaway from the cartridge housing 304 (and thus toward the sample carrier54) to selected extended positions. Depending on the design and locationof the cartridge support 52, the cartridge support 52 may also includean opening to accommodate the extension of the luminescence detector 308toward the sample carrier 54. To actuate and control the movement of theluminescence detector 308, the luminescence cartridge 300 includes adetector driver (or drive mechanism, or drive assembly) 204 that iscoupled to the luminescence detector 308. The detector driver 204 may bemounted at the cartridge housing 304 in any suitable manner, and intypical embodiments is contained within the interior of the cartridgehousing 304. As appreciated by persons skilled in the art, the detectordriver 204 may have any configuration suitable for moving (i.e.,retracting and extending) the luminescence cartridge 300 to any selectedposition relative to the cartridge housing 304 (and thus relative to thesample carrier 54 and any selected sample 16 supported by the samplecarrier 54). In a typical embodiment, the detector driver 204 includes amotor (e.g., a micromotor) coupled to a linkage or transmission that isin turn coupled to the luminescence detector 308. The detector driver204 may include bearings or other appropriate components necessary forfacilitating reliable and accurate actuation of the luminescencedetector 308. The linkage or transmission may have any configurationsuitable for converting the rotational movement of the motor to linearmovement of the luminescence detector 308. For example, the linkage ortransmission may include a set of gears such as a rack and pinion, a setof bevel gears, a worm and worm gear, etc.

To facilitate loading of luminescence cartridge 300 on the cartridgesupport 52 and subsequent removal therefrom, and to prevent damage tothe luminescence detector 308 during loading and removal, theluminescence detector 308 may be fully retractable within the cartridgehousing 304 by the detector driver 204 such that no part of theluminescence detector 308 extends outside of the cartridge housing 304.The luminescence detector 308 may also be moved to the fully retractedposition while the cartridge support 52 is moving the luminescencedetector 308 (and any other cartridges loaded on the cartridge support52) to different positions within the apparatus housing 50. However, theluminescence detector 308 typically does not to be moved when acquiringluminescence data from multiple samples 16. That is, as noted elsewheremultiple samples 16 may be provided at individual sites of a samplesupport 17, such as in different wells of a multi-well plate that issupported on the sample carrier 54. The luminescence detector 308 may bemoved to a desired distance from the first sample 16 which, in theillustrated “top reading” example, is a desired elevation above thefirst sample 16. This desired distance will typically be the same forall samples 16 contained on the sample support 17. Thus, the position ofthe luminescence detector 308 typically does not need to be adjusted asthe sample carrier 54 moves the sample support 17 to sequentially alignone sample 16 after another with the luminescence detector 308 to takesequential luminescence readings.

In the illustrated embodiment, the luminescence detector 308 isgenerally elongated between a proximal end and a distal end. In typicalembodiments, the luminescence detector 308 is cylindrical with acircular cross-section, although in other embodiments may have apolygonal (e.g., rectilinear) cross-section. As an example, theluminescence detector 308 may have a length of 75 mm and an outerdiameter of 11 mm. It will be understood, however, that this example isnot limiting and the luminescence detector 308 may have any sizesuitable for use with the luminescence cartridge 300 and associatedapparatus 12. The distal end (or optical output end) serves as theoptical input of the luminescence detector 308 at which luminescentlight 206 emitted from the sample 16 is received. The proximal end intypical embodiments remains in the cartridge housing 304 throughout theextent of travel of the luminescence detector 308. The luminescencedetector 308 includes an active detector component 312 that receives theluminescent light 206 via the optical input.

An advantage of integrating the luminescence detector 308 with thecartridge housing 304, as opposed to utilizing the output detector 36located external to the luminescence cartridge 300 (as in, for example,FIG. 2), is that it enables the luminescence detector 308 to beconfigured for dedicated operation in conjunction with luminescencemeasurements. That is, unlike the externally located output detector 36,the integrated luminescence detector 308 does not need to accommodatethe operation of any other removable cartridge that might be loaded inthe apparatus 12. Because the luminescence detector 308 is not utilizedfor a broader variety of data acquisitions (e.g., absorbance,fluorescence), the configuration of the luminescence detector 308 may beoptimized for operation specifically with luminescence measurements.Thus, for example, the luminescence detector 308 may be selected to havemaximum sensitivity to the wavelength ranges typically associated withthe luminescent light 206. As an example, the wavelength of theluminescent light 206 may range from visible wavelengths to about 800nm.

Examples of suitable detector components 312 include, but are notlimited to, photomultiplier tubes (PMTs) and photodiodes. For manyapplications, a PMT may be considered to be a preferred type of detectorcomponent 312 in view of its relatively low cost, high gain, highfrequency response, large numerical aperture, and capability for singlephoton counting. As appreciated by persons skilled in the art, the PMTtypically includes a series of electrodes enclosed in an evacuated glasstube, for example a photocathode located at the optical input end of thetube, followed by a series of dynodes, and followed by an anode. One ormore focusing electrodes may be located between the photocathode and thefirst dynode. The anode is in signal communication with an electricalconnector located at the output end of the glass tube, typically via asealed electrical feed-through structure. In the illustrated embodiment,the luminescence detector 308 also includes an outer detector housing316 that encloses and thus protects the detector component 312. Thedetector housing 316 provides a robust structure to which the detectordriver 204 may be directly coupled.

At the proximal end, the luminescence detector 308 may include anelectrical connector 320 (e.g., contacts, terminals, pins, wire support,etc.), which may be part of or mounted to the detector housing 316. Thedetector component 312 is in signal communication with the electricalconnector 320 to enable measurement signals generated by theluminescence detector 308 to be outputted to signal processing circuitry(e.g., data acquisition circuitry) located external to the luminescencecartridge 300. In some embodiments, the detector component 312 may beabout as long as the detector housing 316 such that the electricalconnector of the detector component 312 is in direct contact with (or isthe same as) the illustrated electrical connector 320.

In some embodiments, the luminescence detector 308 may include anadjustable iris (or iris assembly) 324 mounted to the detector housing316 at the distal (optical input) end. The adjustable iris 324 may haveany configuration suitable for adjusting the numerical aperture of theluminescence detector 308, and thus the range of angles over which theluminescence detector 308 can receive the luminescent light 206 emittedfrom the sample 16. The adjustable iris 324 is thus useful formaximizing the amount of luminescent light 206 received from the targetsample 16 and for minimizing the stray light received from adjacentsamples 16 (e.g., samples 16 in adjacent wells of a multi-well plate).The adjustable iris 324 is also useful for accommodating different typesand geometries of sample supports 17, for example different multi-wellplate formats (e.g., 96-well, 384-well, 1536-well, etc.), therebyensuring that light input is optimized for different sample supports 17.Adjustment of the iris 324 may also be done in combination withadjustment of the distance of the optical input end of the luminescencedetector 308 from the sample 16 to optimize light input. Various typesof adjustable irises 324 are known to persons skilled in the art. As anexample, the adjustable iris 324 may include a set of overlappingshutters (not shown) that are movable relative to each other to definean opening of variable diameter through which the luminescent light 206passes into the luminescence detector 308. The adjustable iris 324 mayalso include an actuating device (not shown) that moves the shutters.The actuating device may be manual or automated. An automated actuatingdevice may be in signal communication with the electrical connector 320of the detector housing 316 to receive power from the power source 44.

As indicated earlier in this disclosure, loading removable cartridges atthe cartridge support 52 may entail coupling the removable cartridgeswith the cartridge support 52 in such a way as to place certaincomponents of the removable cartridges in signal communication with thepower source 44 and/or the electronic controller (or system controller,or main apparatus controller) 74, as appropriate. As an example,schematically illustrated in FIG. 3, the luminescence cartridge 300includes a first electrical connector 942 and the cartridge support 52includes a second electrical connector 944. The luminescence cartridge300 may be removably engaged with the cartridge support 52 by removablyengaging or coupling the first electrical connector 942 with the secondelectrical connector 944. For this purpose, the first electricalconnector 942 and the second electrical connector 944 may have anysuitable complementary configurations (e.g., plugs and sockets, male andfemale connectors, etc.). The detector component 312, and the adjustableiris 324 if provided and if powered, may communicate with the firstelectrical connector 942 via one or more wires or a ribbon cable 952.The wire(s) or ribbon cable 952 should be of sufficient length toaccommodate the travel of the luminescence detector 308 within thecartridge housing 304. The detector driver 204 may likewise communicatewith the first electrical connector 942 via a wire 954. The secondelectrical connector 944 in turn communicates with the power source 44and the system controller 74, as schematically indicated by respectivedashed lines interconnecting the cartridge support 52 with the powersource 44 and the system controller 74. The dashed lines may representany suitable communication link (wired or wireless). By thisconfiguration, installing the luminescence cartridge 300 at thecartridge support 52 may place the detector driver 204 and adjustableiris 324 in signal communication with the power source 44 and the systemcontroller 74, and the detector component 312 in signal communicationwith the system controller 74, all via the coupling made between thefirst electrical connector 942 and the second electrical connector 944.Additional dashed lines in FIG. 3 depict communication between the powersource 44 and the cartridge support 52 and the sample carrier 54, andbetween the system controller 74 and the cartridge support 52 and thesample carrier 54.

As also schematically illustrated in FIG. 3, the system controller 74may represent one or more modules configured for controlling, monitoringand/or timing various functional aspects of the apparatus 12 and theluminescence cartridge 300 and/or for receiving data or other signalsfrom the apparatus 12 and the luminescence cartridge 300. In typicalembodiments, the system controller 74 a main electronic processor 362providing overall control, and may include one or more electronicprocessors configured for dedicated control operations or specificsignal processing tasks. The system controller 74 may also include oneor more memories and/or databases 364 for storing data and/or software.The system controller 74 may also include a computer-readable medium 366that includes instructions for performing any of the methods disclosedherein. The functional modules of the system controller 74 may comprisecircuitry or other types of hardware (or firmware), software, or both.In the illustrated example, the modules may include one or more of thefollowing: signal processing (or data acquisition) circuitry 368 forreceiving measurement signals from the luminescence detector 308, adetector drive controller 370 for controlling the movement of theluminescence cartridge 300, an iris controller 372 for controlling theadjustment of the iris 324, a cartridge support drive controller forcontrolling the movement of the cartridge support 52, and a samplecarrier drive controller for controlling the movement of the samplecarrier 54. The system controller 74 may also be representative of oneor more types of user interface devices, such as user input devices(e.g., keypad, touch screen, mouse, and the like), user output devices(e.g., display screen, printer, visual indicators or alerts, audibleindicators or alerts, and the like), a graphical user interface (GUI)controlled by software, and devices for loading media readable by theelectronic processor (e.g., logic instructions embodied in software,data, and the like). The system controller 74 may include an operatingsystem (e.g., Microsoft Windows® software) for controlling and managingvarious functions of the system controller 74.

In one embodiment of a method for analyzing a target 14 in a sample 16,the luminescence cartridge 300 is loaded (or installed) on the cartridgesupport 52 to position the luminescence cartridge 300 in the apparatushousing 50 (FIG. 1B). Loading may include opening a panel or door of theapparatus 12 (such as may be located on a side of the apparatus housing50) to access the cartridge support 52. The cartridge support 52 mayfirst be moved to a position at least partially outside the apparatushousing 50, and after the luminescence cartridge 300 is loaded on thecartridge support 52, the cartridge support 52 may then be moved backinto the apparatus housing 50 with the luminescence cartridge 300 loadedthereon. Loading may also entail coupling the first and secondelectrical connectors 342 and 344 as described above to establish pathsfor transmitting power, data and control signals. Before or afterloading the luminescence cartridge 300, the sample 16 is loaded on thesample carrier 54, typically by first loading the sample 16 on a samplesupport 17 and in turn loading the sample support 17 on the samplecarrier 54. A plurality of samples 16 may be loaded together on anappropriate sample support 17 such as a multi-well plate. Ultimately,the cartridge support 52 and the sample support 17 will be positionedrelative to each other such that the sample 16 will be aligned with theluminescence detector 308, either above or below the luminescencedetector 308 depending on the configuration. In the present context,“aligned” means optically aligned, i.e., positioned so as to establishan optical path sufficient for luminescence data acquisition from thesample 16.

The luminescence detector 308 is then moved toward the sample 16 untilits optical input end reaches a desired distance (reading position) fromthe sample 16. An advantage of the integrated luminescence detector 308is it may be moved very close to the sample 16 to be interrogated, thusmaximizing light collection from the target sample 16 and minimizingstray light collection from adjacent samples. In some embodiments, theluminescence detector 308 is equipped with an iris 324 that may beadjusted as needed in preparation for data acquisition. At the readingposition, the luminescence detector 308 receives (collects) theluminescent light 206 emitted from the sample 16. The luminescencedetector 308 converts these optical signals into electrical signals(detector signals, or measurement signals) and transmits the electricalsignals to the signal processing circuitry 368 of the system controller74. In the case of multiple samples 16, the sample carrier 54 may bemoved to sequentially align each additional sample 16 with theluminescence detector 308, whereby luminescence measurements are takenfrom all samples 16 sequentially.

At the completion of making the luminescence measurements, theluminescence cartridge 300, being a modular or removable cartridge asdescribed throughout the present disclosure, may then be removed fromthe cartridge support 52, and thereafter replaced with anotherluminescence cartridge 300 or different type of removable cartridge asdesired. Before moving the cartridge support 52 through the apparatushousing 50 as needed to remove the luminescence cartridge 300, theluminescence detector 308 may be retracted to a position completelyinside the cartridge housing 304 to protect the luminescence detector308 during movement.

The luminescence cartridges 200 and 300 described above may be utilizedin various types of luminescence measurement techniques, including glowluminescence and flash luminescence. These types of measurements may beapplied, for example, in conjunction with apoptosis studies, cAMP(cyclic adenosine monophosphate) quantitation, GPCR (G protein-coupledreceptor) ligand binding, and immunoassaying. Glow luminescence reagents(e.g., luciferase, luciferin) may be added to samples 16 before or afterloading the sample support 17 on the sample carrier 54 and moving thesample carrier 54 into the apparatus housing 50. Dispensing devicessuitable for controllably adding glow luminescence reagents to samples16 are generally understood by persons skilled in the art, and may bemanually operated or automated devices. A dispensing device may be acomponent of the apparatus 12, in which case it may be controlled by thesystem controller 74, or it may be a device separate from the apparatus12. Flash luminescence reagents (e.g., aequorin or other photoprotein)may be dispensed by an injector provided with the apparatus 12 or aninjector integrated with a removable cartridge. Examples of the use ofluminescence cartridges 200 and 300 for flash luminescence are describedbelow in conjunction with FIG. 8.

Referring now to FIG. 4, another embodiment of the invention, acartridge system 220 for use in an apparatus 12 for analyzing a targetin a sample (not shown) is provided. As shown in FIG. 4, the apparatus12 has a cartridge support 232 (i.e., a slide mechanism or cartridgeslider) which is configured to concurrently receive a multitude ofdifferent cartridges. According to this embodiment, a cartridge for adesired application, such as fluorescence, absorbance, or luminescence,is selected by the user and is selectively aligned by the apparatus 12with the read head 28 and the output detector 36 by moving the selectedcartridge into the analysis position A, along the direction indicated byarrow 234. In this manner, a single instrument may house severalapplication cartridges at a time and an application may be selected bythe user without the user performing a multitude of application specificadjustments to the instrument such as selecting the correct combinationand adjustment of filters, beamsplitters, apertures, and lightguides,etc. for a given application.

Referring again to FIG. 4, the cartridge system 220 comprises aplurality of cartridges, each cartridge being removably engaged with theapparatus 12. Examples of cartridges that may be used in the cartridgesystem 220 may include one or more of the cartridges described herein.Exemplary cartridges used in the cartridge system 220 are shown in FIG.4 as cartridge 222, cartridge 224, cartridge 226, cartridge 228, andcartridge 230. However, a greater or fewer number of cartridges may beused in the cartridge system 220 and the cartridges need not have thesame dimensions such that cartridges having more complex systems (andlarger dimensions) or less complex systems (and smaller dimensions) maybe used in the apparatus 12. The apparatus 12 has a cartridge support232 (i.e., a slide mechanism or cartridge slider) which is configured toreceive the cartridges (e.g., cartridges 222, 224, 226, 228, and 230)and align each of the cartridges with the detector 36 and read head 28.

In some embodiments, each cartridge has indicia, such as an electricallyerasable programmable read-only memory, EEPROM, that indicates the typeof detection that the cartridge can be used for and the correspondingparameters for the particular cartridge. In some embodiments, thecartridge support 232 features a cartridge detector, such as a data linefunction, or an electronic bus system, that enables the instrumentcontrol software (not shown) to identify a cartridge's slot position(i.e., the position of the cartridge on the cartridge support 232) andrecognize any application specific parameters stored in the cartridge'sEEPROM.

In some embodiments, the cartridge support 232 dimensions are such thatit can be moved through a front door or access panel of the apparatushousing and every cartridge position or “slot” on the cartridge support232 can be accessed for installation or removal of a cartridge. In someembodiments, one cartridge is capable of being removed from thecartridge support 232 and exchanged with a second cartridge, oralternately, a new cartridge is installed in an empty slot on thecartridge support 232 without the use of mechanical tools, or with asimple mechanical tool, such as for releasing a fastening mechanism(e.g., a fastening clip).

In some embodiments, at least one of the cartridges in the cartridgesystem 220 has one or more light sources that produces an excitinglight, such as certain cartridges described herein. In some embodiments,at least one of the cartridges in the cartridge system 220 has anintegrated read head and a driver (not shown) for moving the read head,such as certain cartridges described herein. In some embodiments, atleast one of the cartridges in the cartridge system 220 is aluminescence cartridge such as described herein.

Referring now to FIG. 5, in another embodiment, a top and bottom readingcartridge system 240 for use in an apparatus 12 for analyzing a target14 in a sample 16 is provided. As shown in FIG. 5, the apparatus 12 hasa first cartridge support 232 which supports a first cartridge 242 and asecond cartridge support 244 which supports a second cartridge 246. Thefirst and second cartridges 242 and 246 may be any of those describedherein. As noted above in the description relating to FIGS. 1B and 1C,the first cartridge support 232 and/or the second cartridge support 244may be configured for supporting a plurality of cartridges, and forselectively aligning one or more of the cartridges with the read head 28or 250 and/or the detector 36, as appropriate for carrying out aparticular type of measurement.

According to the embodiment shown in FIG. 5, the first cartridge support232 and first cartridge 242 are positioned above the sample support 17.The exciting light 20 from the first cartridge 242 is directed to thesample 16 through a first read head 28. The emitting light 32 from thesample 16 is then directed again through the first cartridge 242, bywhich the emitting light 32 is directed to the detector 36 as previouslydescribed herein, and/or as described in above-referenced U.S. Pat. No.8,119,066. The emitting light 32 may be split into one or morewavelength bands 32 a and 32 b as previously described. The secondcartridge support 244 and second cartridge 246 are positioned below thesample support 17 and the exciting light 248 from the second cartridge246 is directed to the sample 16 through a second read head 250. Theemitting light 252 is then directed again through the second cartridge246, where it is split into emitting lights 252 a and 252 b and relayedremotely to the detector 36. In some embodiments, light guides 254 and256 relay the emitting light 252 a and 252 b from the bottom of thesecond cartridge 246 through an exit port (not shown) to the detector36.

In some embodiments, a luminescence cartridge 200 or 300 such asdescribed above and illustrated in FIG. 2 or 3 is loaded at the firstcartridge support 232 and thus above the sample support 17 for topreading, or is loaded at the second cartridge support 244 and thus belowthe sample support 17 for bottom reading, or two luminescence cartridges200 or 300 may be respectively loaded at the first cartridge support 232and second cartridge support 244.

The design of the first and second cartridges 242 and 246 is independentof whether the cartridge is positioned either above or below the samplesupport 17. However, when the cartridge configuration shown in FIG. 5 isused, a movable detector port support 258 (e.g., a slide or selectorwheel mechanism) is used which switches the detector 36 from seeingeither emitting light 32 a and 32 b from the first cartridge 242 andfirst read head 28 or seeing emitting light 252 a and 252 b from thesecond cartridge 246 and second read head 250. The emitting light 252 aand 252 b exiting the light guides 254 and 256 is reflected into thedetector 36 by mirrors 260 a and 260 b. The selection between the firstand second cartridges 242 and 246 is done by moving the movable detectorport support 258 along an axis 262 perpendicular to the detector 36.This embodiment is further detailed in FIG. 6.

According to the embodiment shown in FIG. 6, the movable detector portsupport 258 is located in the gap between the exit of the firstcartridge 242 and the entrance to the detector 36. The movable detectorport support 258 houses an aperture 264 (e.g., a beam pass) whichdirects emitting light 32 a and 32 b from the first cartridge 242 and abeam stop/shutter 266 which protects the detector 36 when the instrumentfront door is opened, such as for maintenance or to exchange acartridge. The movable detector port support 258 may also be equippedwith light attenuating filters 268 and 270 which enable the system toanalyze a signal that is too strong for the detector 36. The movabledetector port support 258 may also be equipped with a constant low powerlight source in order to monitor the function and performance of thedetector 36 over longer periods of operation (not shown). The lightsource resident in the detector port support 258 may be built from a LEDand stabilized by feedback from a photodiode, as described inabove-referenced U.S. Pat. No. 8,119,066. The LED output is attenuateddown to levels acceptable to the detector 36 by help of a diffusingglass. Another position along the movable detector port support 258 mayhouse mirrors 260 a and 260 b that reflect the emitting light 252 a and252 b exiting the light guides 256 and 254 from above and below themovable detector port support 258. Emitting light 252 a and 252 bexiting the light guides 256 and 254 can enter the detector 36 when theposition of the light guides 256 and 254 on the detector port support258 is aligned with the detector 36.

Referring now to FIG. 7, another embodiment of the invention, a flashfluorescence cartridge system 280 for use in an apparatus 12 foranalyzing a target 14 in a sample 16 is provided. The flash fluorescencecartridge system 280 has an injector cartridge (i.e., the firstcartridge 282) that may be used for flash fluorescence applications,which require injection of a starter reagent in combination withimmediate fluorescence reading.

For typical flash fluorescence applications, clear bottom microplatesare frequently used as the sample support 17 (i.e., a sample supporthaving an aperture 58) such that injection of the reagent occurs fromabove the well and fluorescence is measured simultaneously from belowthe sample holder 17. Accordingly, FIG. 7 uses the top and bottomreading cartridge configuration, which has been described with respectto FIG. 5. According to the embodiment shown in FIG. 7, an injectorcartridge 282 is installed as the first cartridge (i.e., the uppercartridge) on the first cartridge support 232. A second cartridge 246 ispositioned on a second cartridge support 244. The second cartridge 246may be any of those described herein such as certain cartridgesdescribed herein and/or in above-referenced U.S. Pat. No. 8,119,066, butconfigured for a fluorescence application. As noted again, the firstcartridge support 232 and/or the second cartridge support 244 may beconfigured for supporting a plurality of cartridges, and for selectivelyaligning one or more of the cartridges with the read head 250 and/or thedetector 36, as appropriate for carrying out a particular type ofmeasurement.

As shown in FIG. 7, the first cartridge 282 features a reagent reservoir284, a pump 286, and a tubing system 288 connected to a nozzle 290(which may be rigid). The nozzle 290 can be driven down from within thefirst cartridge 282 to approach the sample support 17 from above, asshown by arrow 292. The nozzle 290 is aligned with a sample 16 and readhead 250 and reagent 294 is delivered to the sample 16 via the nozzle290. Exciting light 248 and emitting light 252 is directed to the sample16 and subsequently to the detector 36 as described with respect to FIG.5. Sample measurement may take place before, during, and after injectionof reagent 294.

Using an injector module that can be easily removed under routineoperating conditions, such as the injector cartridge described herein,provides several advantages. The injector cartridge and external dockingstation may also be used as a precision dispenser apparatus. Inaddition, the cartridge's tubing system can be easily rinsed/cleaned bythe customer and primed, i.e., floated, thereby removing bubbles, withthe reagent outside of the instrument enclosure. This may occur with theinjector cartridge still plugged into the cartridge support, but withthe cartridge support moved through the instrument door and having awaste reservoir placed underneath. Priming may also occur with theinjector cartridge removed from the cartridge support and plugged into adocking station. Both strategies reduce the risk of accidentallyfloating the interior of the apparatus with reagent. Also, the output ofthe injector cartridge can be calibrated for the customer's solvents atthe customer site using an external docking station mounted on top ofweighing scales.

Referring now to FIG. 8, another embodiment of the invention, a flashluminescence cartridge system 800, for use in an apparatus 12 foranalyzing a target in a sample (not shown) is provided. Measurement offlash type luminescence requires the injection of a starter reagent (orflash luminescence reagent), and measurement of luminescence light at afraction of a second later. The configuration of the cartridge system800 for this application may include an injector cartridge 282, asdescribed with respect to FIG. 7 and a luminescence cartridge 200 asdescribed with respect to FIG. 2. The injector cartridge 282 and theluminescence cartridge 200 are positioned on adjacent slots on thecartridge support 232 as described with respect to FIG. 4. Anycombination of cartridges may be possible (including multipurposecartridges as described, for example, in above-referenced U.S. Pat. No.8,119,066). However, the cartridges are typically dedicated to a single(or only few) applications, unless the required performance would not becompromised by including an additional application. In some embodiments,due to the proximity of the injection position and the read position,the luminescence cartridge 200 and the injector cartridge 282 are fusedinto a single, dual slot cartridge.

As shown in FIG. 8, the luminescence cartridge 200 is aligned with thedetector 36 and detects emitting light 32 from a first target 14 a (notshown) on the sample support 17, which is positioned below the cartridgesupport 232. A flash type luminescence measurement is performed by firstaligning the luminescence cartridge 200 with the detector 36 in theanalysis position indicated in FIG. 8. The cartridge support 232 is thenin a fixed position until the sample analysis is complete. The samplesupport 17 is then moved to align the first sample 16 a (not shown) withthe injector cartridge 282 in a first position, i.e., an “injectingposition,” position A. Starter reagent is then injected onto the firstsample 16 a. After the starter reagent is injected, the sample support17 is then moved such that the first sample 16 a on the sample support17 is in a second position i.e., a “reading position,” position B, wherethe first sample 16 a is aligned with the luminescence read head (notshown) within the luminescence cartridge 200. A measurement may be takenon a second sample 16 b (not shown) by moving the sample support 17 tothe injecting position, i.e., the “injecting position,” position A,below the injector cartridge 282 and injecting starter reagent onto thesecond sample 16 b. The sample support 17 is then moved such that thesecond sample 16 b on the sample support 17 is in the second positioni.e., the “reading position,” position B, where the second sample 16 bis aligned with the luminescence read head (not shown) within theluminescence cartridge 200.

According to another embodiment, the luminescence cartridge 300described above and illustrated in FIG. 3 is utilized in the flashluminescence cartridge system 800, in place of the luminescencecartridge 200. In some embodiments, the luminescence cartridge 300 andthe injector cartridge 282 may be integrated together as a single, dualslot cartridge. The flash luminescence cartridge system 800 may beoperated with the luminescence cartridge 300 in generally the samemanner as described above and illustrated in FIG. 8 in connection withthe luminescence cartridge 200. However, as the luminescence cartridge300 includes an integrated luminescence detector 308 (FIG. 3) instead ofa separate read head 202 and external output detector 36 (FIG. 2), theluminescence cartridge 300 does not need to be aligned with the outputdetector 36. For each sample 16 being interrogated, the sample carrier54 is simply moved to the injection position A to align the sample 16with the injector cartridge 282 and inject the starter reagent, and thenmoved to the reading position B to align the sample 16 with theluminescence detector 308 and take the luminescence measurements forthat particular sample 16.

FIGS. 9A and 9B are schematic top side views, respectively, of anotherexample of a sample analyzing system or apparatus 900 according to someembodiments. FIG. 9B is a schematic side view of the sample analyzingapparatus 900 illustrated in FIG. 9A. The sample analyzing apparatus 900includes a cartridge carrier 902 configured to support one or moreapplication cartridges (and/or interface cartridges) 904. The cartridgecarrier 902 and application cartridges 904 may be designed to providesupport for existing applications and technologies, such as for example,applications and cartridges provided by the SpectraMax® Paradigm™ andSpectraMax® i3™ systems available from Molecular Devices, LLC,Sunnyvale, Calif., USA. The application cartridges 904 may also befuture cartridges configured to operate with a common form factordictated by an interface cartridge that may operate as an applicationcartridge as described below.

The sample analyzing apparatus 900 also includes a sample support 906,which is shown in FIGS. 9A and 9B as being positioned underneath abottom plate 909 of the sample analyzing apparatus 900 and inside anincubation chamber 938. The sample support 906 may be implemented as acarrier for multiple samples removably mounted on an x-y transport. Thesamples may be placed in sample holders or wells arranged on a planartray structure. In the example implementations described herein, themultiple sample holder is implemented using a microplate, which is knownin the art as a sample holder typically used in detection systems. Thereference herein to a microplate is not however intended as limiting.Those of ordinary skill in the art would understand that other suitablesample holders may be used as well. It is to be understood that thesample support 906 refers to the microplate and x-y transport as a unitin this description.

The sample analyzing apparatus 900 includes a light source implementedusing a flash lamp module 910, and an LED wheel 928. The flash lampmodule 910 or an LED on the LED wheel 928 generates an excitation lightalong an excitation light path 941, which is directed through the systemusing directing optics devices strategically placed in the systemhousing. Directing and selecting optics, such as an excitation lightsplitter 913, may be controlled to guide a selected excitation lightfrom either the flash lamp module 910 or the LED wheel 928. The flashlamp module 910 may be any suitable flash lamp, such as a Xenon flashlamp, and an interface for controlling on/off state, duty cycle, and anyother parameters that may be advantageously controlled for theapplications performed by the system 900. The LED wheel 928 includes aplurality of high-powered LEDs positioned on the periphery of the LEDwheel 928, which may be rotated using a motor to insert the selected LEDin the excitation light path 941.

The detection devices are implemented in the sample analyzing apparatus900 using an absorbance detector (such as a photodiode, for example)mounted on an absorbance reader module 917 in FIG. 9B, a first PMT 912,and a second PMT 914. The absorbance read head 917, a bottomfluorescence optics module 915, and a function expander module 908 maybe mounted under the bottom plate 909 of the housing. In addition, asshown in FIG. 9B, the absorbance reader module 917, the bottomfluorescence optics module 915, and the function expander module 908 aremounted under the incubation chamber 938, which holds the sample support906.

The bottom plate 909 may include four openings. A first opening 911 aprovides access for an excitation light along an excitation optical pathaligned with an absorbance lens assembly 913 a and a sample on thesample carrier to perform absorbance measurements. A second opening 911b in the bottom plate 909 provides access for optical paths formed fortop-side fluorescence and luminescence measurements and aligned with atop fluorescence/luminescence lens assembly 913 b. A third opening 911 cin the bottom plate 909 may be used to insert a light guide into theincubation chamber 938 in close proximity to a selected sample in thesample carrier that may be used to receive luminescence emission lightin accordance with specific applications. A fourth opening 911 d in thebottom plate 909 may be used for access by components in the functionexpander module 908. In an example implementation, the function expandermodule 908 may be an imaging system interface that permits a cellimaging system under the multimode reader 900 to use resources availableon a cartridge, such as illuminating functions or fluid injectionfunctions as described below.

The first PMT 912 may be a standard photomultiplier tube that may beused in most applications performed by the sample analyzing apparatus900. The second PMT 914 may be a specialized photomultiplier tube suchas for example a UV/VIS (for measuring ultraviolet as well as visiblelight) or a UV/VIS/NIR (for measuring ultraviolet or near infrared aswell as visible light). The second PMT 914 may be designated as optionalin example implementations such that it is installed per customerspecification.

The sample analyzing apparatus 900 includes an excitation monochromator930 and an emission monochromator 932 configured to receive a light andto transmit the light at a selected wavelength. The sample analyzingapparatus 900 also includes an optical configuration panel 936 that maybe used to configure the direction and characteristics of the opticalpaths between light source and detectors, and to control lighttransmission into and out of the excitation monochromator 930 andemission monochromator 932. The optical configuration panel 936 mayinclude a first set of optical ports 940 for directing the excitationlight path 941 to and from the excitation monochromator 930 and a secondset of optical ports 942 for directing an emission light path to andfrom the emission monochromator 932.

The excitation monochromator 930 may be controlled to spread thereceived excitation light into its component wavelengths and to output aselected one of the wavelengths along the excitation light path 941.Particular applications may operate with an excitation light at aparticular wavelength. The excitation monochromator 930 may receive thegenerally white light generated by the flash lamp module 910 and outputsthe excitation light at the wavelength selected for the application.

The excitation monochromator 930 and the emission monochromator 932 maybe implemented as double stacked gratings configured as a subtractingdouble monochromator. The excitation monochromator 930 and the emissionmonochromator 932 may be enclosed in a substantially wall-off chamberthat may include a middle plate 168 between the top and bottom gratingsof each monochromator.

Particular applications may also require measurement of an emitted lightfrom a sample at a selected wavelength. The emitted light from thesample may be directed to the second set of optical ports 942. An inputemission light 946 is directed from the second set of ports 942 to theemission monochromator 932. The emission monochromator 932 directs theselected wavelength component of the emission light 942 to the secondset of ports 942 towards optics that directs the emission light towardsa selected detector.

In the example implementation described here with reference to FIGS. 9Aand 9B, the excitation monochromator 930 and emission monochromator 932may be implemented as top and bottom level monochromators. For example,in FIG. 9B, the emission monochromator 932 includes a top level thatreceives the emission light 946 at an emission monochromator entranceslit 960 on the optical configuration panel 936. The top level of theemission monochromator 932 includes a top grating, which spreads theemission light on the emission light path 946 into multiple light pathseach at the component wavelengths of the emission light. A mirror on theoptical configuration panel 936 is positioned at an angle for receivingthe selected wavelength component of the emission light. The selectedwavelength component of the emission light is directed to another mirroron the optics configuration pane, which directs the emission light tothe lower level grating of the emission monochromator 932. The emissionlight is again spread into its component wavelengths, which may belimited substantially to the wavelength selected for the top level ofthe emission monochromator 932. The lower level of the emissionmonochromator 932 is positioned to place the selected wavelengthcomponent of the emission light at an emission monochromator exit slit962.

The emission monochromator entrance slit 960 and emission monochromatorexit slit 962 accommodate the two-level grating structure of theemission monochromator 932. The dual-level optical path optionsavailable using the emission monochromator entrance slit 960 andemission monochromator exit slit 962 may also accommodate a dual-channeloptical path format of the cartridges used as application and/orinterface cartridges 904.

Application cartridges may be used to perform measurements according toexisting applications available prior to an implementation of the sampleanalyzing apparatus 900, or after to conform to the sample analyzingapparatus 900. An interface cartridge may be used to performmeasurements using a variety of detection modes. Accordingly, the term“interface cartridge 904” is used in place of the term “applicationand/or interface cartridge 904” except where the context warrants theuse of the term “application and/or interface cartridge 904.”

The interface cartridge 904 includes optical components arranged toprovide multiple paths for excitation and emission light paths that areselectable according to specific applications, or more specifically,specific detection modes. For example, the interface cartridge 904 maybe moved to a position that guides the excitation light path 944 exitingthe excitation monochromator 930 to the sample on the sample support 906for an absorbance measurement. The interface cartridge 904 may alsoinclude an optics path that guides the excitation light path 944 throughfluorescence measurement optics, which directs the excitation light tothe sample and the emission light generated by the sample to one of thedetectors.

The interface cartridge 904 may be used in conjunction with a slidingswitch mechanism 920 to configure optics paths between light source anddetectors for applications that involve using monochromators, the flashlamp module 910, the LED wheel 928 and any of the detectors (photodiodeand PMTs). The interface cartridge 904 and the sliding switch mechanism920 are movable to enable positioning the interface cartridge 904 andthe sliding switch mechanism 920 in position to provide a desired lightpath. The interface cartridge 904 may be moved by positioning thecartridge carrier 902, and the sliding switch mechanism 920 may be movedby a motor in conjunction with a sliding switch guide rail 922.

As one non-limiting example of a configuration, FIG. 1A illustrates thatthe sliding switch mechanism 920 is selectively movable to fivedifferent positions A, B, C, D, and E. At position A, the sliding switchmechanism 920 blocks light to the PMTs 912 and/or 914 when not beingutilized for detection. At position B, emission light received from abottom fluorescence measurement via suitable optics (e.g., an emissionfiber) is directed to the first PMT 912. At position C, an uppercartridge light path is directed to the first PMT 912 without utilizingthe emission monochromator 932. At position D, one or more light pathsmay be formed: a top interface cartridge light path may be directed tothe second PMT 914; a lower application (non-interface) cartridge lightpath may be directed to the first PMT 912; top and lower application(non-interface) cartridge light paths may be directed to the second PMT914 and the first PMT 912, respectively; and a top application(non-interface) cartridge light path may be directed to the second PMT914. As further examples in the case of luminescence measurement,position C may be utilized to direct luminescence light emitted from asample to the first PMT 912, and position D may be utilized to directluminescence light emitted from a sample to the second PMT 914.

Referring to FIG. 9B, the bottom fluorescence optics module 915 includesa bottom fluorescence read head positioned below the sample support 906,which in turn is positioned below the bottom plate 909. By thisconfiguration, the bottom fluorescence read head may be utilized todirect excitation light to the sample from below the sample support 906,and/or receive fluorescence light emitted from the sample from below thesample support 906. Suitable optics, such as an excitation fiber andemission fiber extending from the optics configuration panel 936, may becoupled to the bottom fluorescence optics module 915 to route excitationlight to the bottom fluorescence read head from an appropriate lightsource, and to route emission light from the bottom fluorescence readhead to an appropriate detector.

Additional details regarding various embodiments consistent with thesample analyzing apparatus 900 described above in conjunction with FIGS.9A and 9B are described in above-referenced U. S. Patent ApplicationPub. No. 2014/0191138.

FIG. 10 is a schematic view of another example of a sample analyzingsystem or apparatus 1600 according to some embodiments. The sampleanalyzing apparatus 1600 may generally include an apparatus housingenclosing various components of the sample analyzing apparatus 1600.FIG. 10 illustrates a front wall 1606 (or portion thereof) and a bottomwall 1608 (or portion thereof) of the apparatus housing. The sampleanalyzing apparatus 1600 may also generally include a movable cartridgesupport 1612 configured for supporting one or more cartridges, and amovable sample carrier 1614 for supporting one or more samples 1616under investigation or for supporting a sample support 1618 that holdsor contains such samples 1616. For example, the sample support 1618 maybe an optical plate providing a plurality of wells 1620 containingindividual samples 1616. The cartridge support 1612 may be movablebetween an inside cartridge support position (as illustrated) at whichthe cartridge support 1612 is positioned entirely in the apparatushousing, and an outside cartridge support position at which thecartridge support 1612 is positioned at least partially outside theapparatus housing to facilitate loading of one or more cartridgesthereon. Similarly, the sample carrier 1614 may be movable between aninside sample carrier position (as illustrated) at which the samplecarrier 1614 is positioned entirely in the apparatus housing, and anoutside sample carrier position at which the sample carrier 1614 ispositioned at least partially outside the apparatus housing tofacilitate loading of one or more samples 1616 (or a sample support 1618holding one or more samples 1616) thereon. The sample analyzingapparatus 1600 may also generally include one or more optical detectors1624 configured for collecting optical detection signals from one ormore different types of cartridges operatively loaded on the cartridgesupport 1612. Generally, the structure and operation of any or all ofthe foregoing components of the sample analyzing apparatus 1600 may beconsistent with those described above in conjunction with otherembodiments disclosed herein.

FIG. 10 also illustrates an example of a luminescence cartridge 1628according to some embodiments. Like other cartridges described above,the luminescence cartridge 1628 is sized and configured to be removablyloaded (i.e., mounted or installed) on the cartridge support 1612, andmay be replaced or exchanged with other cartridges of the same ordifferent type as desired. The luminescence cartridge 1628 includes acartridge housing 1632 and an injector assembly 1636 at least partiallydisposed in the cartridge housing 1632 and movable through an opening1638 of the cartridge housing 1632. In typical embodiments, the injectorassembly 1636 is linearly movable in a reciprocating manner, theinjector assembly 1636 may be alternately extended and retracted. Hence,the injector assembly 1636 is movable alternately toward and away fromthe cartridge housing 1632, and thus alternately toward and away fromthe sample carrier 1614 and any sample 1616 with which the injectorassembly 1636 is operatively aligned. Depending on the design andlocation of the cartridge support 1612, the cartridge support 1612 mayalso include an opening to accommodate the movement of the injectorassembly 1636.

To actuate and control the movement of the injector assembly 1636, theluminescence cartridge 1628 includes a driver 1642 (or drive mechanism,or drive assembly) that is coupled to the injector assembly 1636. Thedriver 1642 may be mounted at the cartridge housing 1632 in any suitablemanner, and in typical embodiments is contained within the interior ofthe cartridge housing 1632. As appreciated by persons skilled in theart, the driver 1642 may have any configuration suitable for moving(i.e., retracting and extending) the injector assembly 1636 to anyselected position relative to the cartridge housing 1632 (and thusrelative to the sample carrier 1614 and any selected sample 1616supported thereon). In a typical embodiment, the driver 1642 includes amotor (e.g., a micromotor) coupled to a linkage or transmission that isin turn coupled to the injector assembly 1636. The driver 1642 mayinclude bearings or other appropriate components necessary forfacilitating reliable and accurate actuation of the injector assembly1636. The linkage or transmission may have any configuration suitablefor converting the rotational movement of the motor to linear movementof the injector assembly 1636. For example, the linkage or transmissionmay include a set of gears such as a rack and pinion, a set of bevelgears, a worm and worm gear, etc.

To facilitate loading of luminescence cartridge 1628 on the cartridgesupport 1612 and subsequent removal therefrom, and to prevent damage tothe injector assembly 1636 during loading and removal, the injectorassembly 1636 may be fully retractable within the cartridge housing 1632by the driver 1642 such that no part of the injector assembly 1636extends outside of the cartridge housing 1632. The injector assembly1636 may also be moved to the fully retracted position while thecartridge support 1612 is moving the injector assembly 1636 (and anyother cartridges loaded on the cartridge support 1612) to differentpositions within the apparatus housing. However, the injector assembly1636 typically does not need to be moved when acquiring luminescencedata from multiple samples. That is, as noted elsewhere multiple samplesmay be provided at individual sites of a sample support 1618, such as indifferent wells 1620 of a multi-well plate that is supported on thesample carrier 1614. The injector assembly 1636 may be moved to adesired distance from the first sample 1616 which, in the illustrated“top reading” example, is a desired elevation above the first sample1616. This desired distance will typically be the same for all samplescontained on the sample support 1618. Thus, the position of the injectorassembly 1636 typically does not need to be adjusted as the samplecarrier 1614 moves the sample support 1618 to sequentially align onesample after another with the injector assembly 1636 to take sequentialluminescence readings.

In some embodiments, the sample analyzing apparatus 1600 may alsoinclude a bottom read head 1615, which may be appropriately coupled tooptics and operate as generally described elsewhere in the presentdisclosure. The bottom read head 1615 may be optically aligned with theinjector assembly 1636. This configuration enables injection from topand bottom fluorescence reading at the same time.

FIG. 11 is a perspective view of an example of the injector assembly1636 according to some embodiments. The injector assembly 1636 includesan injector housing 1646 generally elongated between a proximal end 1748and a distal end 1750 of the housing 1646. In typical embodiments, theinjector housing 1646 is cylindrical with a circular cross-sectionalthough in other embodiments may have a polygonal cross-section. Theinjector assembly 1636 includes a light guide 1754 and one or moreinjector needles 1756 and 1758 (two in the illustrated embodiment)extending through the injector housing 1646 generally in parallel witheach other. In some embodiments, the injector assembly 1636 includes alight guide 1754 extending through the injector housing 1646 generallyin parallel with the injector needles 1756 and 1758. In suchembodiments, the injector assembly 1636 may also be referred to as aninjector/reader assembly. The light guide 1754 and injector needles 1756and 1758 may extend all the way down to the distal end 1750 or mayterminate at a small distance short of the distal end 1750. The lightguide 1754 is configured for transmitting luminescent light emitted fromthe sample 1616 to a luminescence detector. For this purpose, the lightguide 1754 may be an optical fiber, a light pipe, etc. The injectorneedles 1756 and 1758 are configured for dispensing fluid onto thesample 1616 (e.g., into selected wells 1620 of the sample support 1618),such as reagents as may be utilized for glow luminescence or flashluminescence as appreciated by persons skilled in the art. Theintegration of the light guide 1754 and the injector needles 1756 and1758 into the single injector assembly 1636 particularly facilitatesflash luminescence. Moreover, the provision of two or more injectorneedles 1756 and 1758 facilitates the use of different types ofreagents. For example, the first injector needle 1756 may dispense afirst reagent and the second injector needle 1758 may dispense a secondreagent. In one specific, yet non-limiting example, the first reagentmay be firefly luciferase and the second reagent may be Renillaluciferase. Hence, the distal end 1750 of the injector assembly 1636 mayserve both as an optical input and a fluid output of the injectorassembly 1636.

Referring back to FIG. 10, luminescent light directed into the injectorassembly 1636 from the sample 1616 is depicted by a dashed arrow 1662,and fluid streams directed out from the injector assembly 1636 from thefirst injector needle 1756 and second injector needle 1758 are depictedby solid arrows 1664 and 1666, respectively. As also shown in FIG. 10,the cartridge housing 1632 may include an optical port 1668 aligned withthe luminescence detector 1624 for enabling the luminescent light to betransmitted to the luminescence detector 1624. The dashed line leadingfrom the injector assembly 1636 to the luminescence detector 1624 mayrepresent light guide 1754 (FIG. 11) extending out from the proximal endof the injector assembly 1636 and to or through the optical port 1668.Alternatively, the light guide 1754 may terminate at some point in thecartridge housing 1632, in which case the dashed line between theinjector assembly 1636 and the luminescence detector 1624 may at leastpartially represent one or more other types of optical components(mirrors, etc.) configured for directing the luminescent light to theluminescence detector 1624. As an alternative to utilizing the externalluminescence detector 1624, the luminescence cartridge 1628 may includean internal detector (not shown) in the cartridge housing 1632 thatcommunicates with electronics of the sample analyzing apparatus 1600outside the luminescence cartridge 1628.

As further shown in FIG. 10, the luminescence cartridge 1628 includesone or more liquid reservoirs (e.g., bottles) such as reagent reservoirs1672 and 1674. The reagent reservoirs 1672 and 1674 may be disposed on areservoir support 1676, which may be movable alternately into and outfrom the cartridge housing 1632 as described below. The one or morereagent reservoirs 1672 and 1674 may fluidly communicate with theinjector assembly 1636 via a pump 1678 (e.g., a pump assembly or pumpsystem). The pump 1678 may represent one or more pumps (or pump units).For example, the first reagent reservoir 1672 may communicate with thefirst injector needle 1756 (FIG. 11) via a first fluid line 1682 (e.g.,tube) to supply a first reagent, and the second reagent reservoir 1674may communicate with the second injector needle 1758 (FIG. 11) via asecond fluid line 1684 to supply a second reagent. The fluid lines 1682and 1684, as well as the light guide 1754, should have a length andflexibility sufficient to accommodate the alternating extension andretraction of the injector assembly 1636.

Referring to FIG. 11, in some embodiments the injector assembly 1636does not include the light guide 1754. In such embodiments luminescentlight emitted from the sample 1616 may, for example, be transmitted tothe bottom read head 1615 positioned below the sample 1616 (i.e., belowthe sample carrier 1614 and sample support 1618 shown in FIG. 10) androuted via appropriate optics (e.g., a light guide such as an opticalfiber) to the luminescence detector 1624. Alternatively, luminescentlight may transmitted directly to a luminescence detector (not shown)positioned below the sample 1616, without utilizing a bottom read head1615 or other transmitting optics.

The luminescence cartridge 1628 may also include electronics 1688configured for communicating with and/or controlling various componentsof the luminescence cartridge 1628. The electronics 1688 may include oneor more circuits and other electrical hardware mounted on one or moresupport substrates such as, for example, printed circuit boards (PCBs).In addition to or as part of the electronics 1688, the luminescencecartridge 1628 may include an electrical connector configured forremovable coupling to the sample analyzing apparatus 1600 (e.g., acomplementary electrical connector of sample analyzing apparatus 1600)to receive power from and transmit signals to or from the sampleanalyzing apparatus 1600, as described above in conjunction with otherembodiments such as that illustrated in FIG. 3. Thus, as described abovethe electrical coupling may be effected by plugs and sockets, male andfemale connectors, etc., whereby certain components of the luminescencecartridge 1628 are placed in signal communication with a power source orsystem controller of the sample analyzing apparatus 1600 as appropriate(e.g., the power source 44 and system controller 74 described above andillustrated in FIG. 3).

An example of a method for analyzing a sample 1616 will now be describedwith reference to FIGS. 10 and 11. The luminescence cartridge 1628 isloaded (or installed) on the cartridge support 1612 to position theluminescence cartridge 1628 in the apparatus housing of the sampleanalyzing apparatus 1600. Loading may include opening a panel or doorsuch as may be located at the front wall 1606 of the apparatus housingto access the cartridge support 1612. The cartridge support 1612 mayfirst be moved to a position at least partially outside the apparatushousing, and after the luminescence cartridge 1628 is loaded on thecartridge support 1612, the cartridge support 1612 may then be movedback into the apparatus housing with the luminescence cartridge 1628loaded thereon. Loading may also entail coupling the luminescencecartridge 1628 with the sample analyzing apparatus 1600 via electricalconnectors as described above to establish paths for transmitting power,data and control signals. Before or after loading the luminescencecartridge 1628, the sample 1616 is loaded on the sample carrier 1614,typically by first loading the sample 1616 on a sample support 1618 andin turn loading the sample support 1618 on the sample carrier 1614. Aplurality of samples 1616 may be loaded together on an appropriatesample support 1618 such as a multi-well plate. Ultimately, thecartridge support 1612 and the sample support 1618 will be positionedrelative to each other such that the sample 1616 will be aligned withthe injector assembly 1636. In the present context, “aligned” meansoptically aligned, i.e., positioned so as to establish an optical pathsufficient for luminescence data acquisition from the sample 1616. Theterm “aligned” may also mean fluidly aligned, i.e., positioned so as tobe able to dispense fluid onto the sample 1616.

The injector assembly 1636 is then moved toward the sample 1616 untilits optical input end reaches a desired distance (reading position) fromthe sample 1616. The injector assembly 1636 may be moved very close tothe sample 1616 to be interrogated, thus maximizing light collectionfrom the target sample 1616 and minimizing stray light collection fromadjacent samples. At the reading position, the pump 1678 is operated toestablish a flow of a selected reagent from one of the reagentreservoirs 1672 or 1674 to the corresponding injector needle 1756 or1758, whereby the selected reagent is injected by the injector needle1756 or 1758 to the sample 1616 to induce luminescence in the sample1616. The light guide 1754 of the injector assembly 1636 receives(collects) the resulting luminescent light 1662 emitted from the sample1616 and transmits the luminescent light 1662 to the luminescencedetector 1624 (or an internal detector provided in the cartridge housing1632, not shown). The luminescence detector 1624 converts these opticalsignals into electrical signals (detector signals, or measurementsignals) and transmits the electrical signals to signal processingcircuitry, such as may be provided by a system controller of sampleanalyzing apparatus 1600, as described above in conjunction with otherembodiments. In the case of multiple samples 1616, the sample carrier1614 may be moved to sequentially align each additional sample 1616 withthe light guide 1754, whereby luminescence measurements are taken fromall samples 1616 sequentially.

In some embodiments, more than one reagent may be utilized for eachsample 1616. For example, the pump 1678 may be establish a flow of afirst reagent from the first reagent reservoir 1672 to the firstinjector needle 1756, after which the light guide 1754 receives theluminescent light 1662 emitted from the sample 1616 in response toinjecting the first reagent. Subsequently, the pump 1678 may beestablish a flow of a second reagent from the second reagent reservoir1674 to the second injector needle 1758, after which the light guide1754 receives the luminescent light 1662 emitted from the sample 1616 inresponse to injecting the second reagent. In some embodiments, thesecond reagent may include a quenching agent that quenches the signalresulting from the first reagent.

At the completion of making the luminescence measurements, theluminescence cartridge 1632, being a modular or removable cartridge asdescribed throughout the present disclosure, may then be removed fromthe cartridge support 1612, and thereafter replaced with anotherluminescence cartridge 1632 or different type of removable cartridge asdesired. Before moving the cartridge support 1612 through the apparatushousing as needed to remove the luminescence cartridge 1632, theinjector assembly 1636 may be retracted to a position completely insidethe cartridge housing 1632 to protect the injector assembly 1636 duringmovement.

The injector system of the sample analyzing apparatus 1600 (i.e., thereservoirs 1672 and 1674, pump 1678, injector needles 1756 and 1758, andassociated fluid lines) need to be rinsed and possibly decontaminatedafter being used to clean the system between experiments as well as toprevent the clogging of fluidic components such as the pump 1678 andfluid lines. In addition, as part of preparing the injector system foruse the user needs to prime the system. The rinsing and priming of thesystem may involve the dispensing of a mixture of liquid and air for alimited amount of time, which may generate bubbles and may also generatemuch larger droplets than the droplets expected for normal dispensingprocedures. To illustrate this, FIG. 12A is a perspective view of thetip (distal) section of the injector assembly 1636 when surfaces areclean and no bubbles are being generated. In this case, liquid streams1664 and 1666 are dispensed from the tips of the injector needles 1756and 1758 in the expected way. By comparison, FIG. 12B is a perspectiveview of the tip (distal) section of the injector assembly 1636 whenbubbles have been generated in the injector system as a result ofdispensing a liquid/air mixture. In this case, liquid may accumulate(possibly as the result of surface tension holding the liquid streamback) and result in the formation of a droplet 1802 of uncontrolledsize. Such a droplet 1802 will eventually separate from the injectorassembly 1636, and then fall down and/or splash onto an undesiredportion of the sample support 1618 (FIG. 11), or onto one or more opticscomponents in the apparatus housing, etc. The droplet 1802 may alsocontaminate the input end of the light guide 1754. In all such cases,the droplet 1802 may contaminate the sample analyzing apparatus 1600and/or cause the experiment to be aborted due to contamination.

To address this problem, in some embodiments the sample analyzingapparatus 1600 and luminescence cartridge 1628 are configured to enablerinsing and priming to be performed outside of the sample analyzingapparatus 1600. In this manner, any unavoidable dispensing of aliquid/air mixture occurs remotely from the internal optics componentsof the sample analyzing apparatus 1600, and all bubbles may be purgedfrom the injector system prior to loading the luminescence cartridge1628 into the apparatus housing of the sample analyzing apparatus 1600.The external rinsing and priming approach will now be described withreference to FIGS. 13A to 15.

FIG. 13A is a top schematic view of the sample analyzing apparatus 1600in which the cartridge support 1612 and the luminescence cartridge 1628loaded thereon are in an inside position, i.e., fully inside theapparatus housing. FIG. 13A corresponds to the operative position of theluminescence cartridge 1628 at which luminescence measurements may betaken, as described above in conjunction with FIGS. 10 and 11. FIG. 13Bis a top schematic view of the sample analyzing apparatus 1600 in whichthe cartridge support 1612 and the luminescence cartridge 1628 loadedthereon are have been moved to an outside position, i.e., extending atleast partially outside of the interior of the apparatus housing. Incomparison to FIG. 10, certain components of the luminescence cartridge1628 have been rearranged for illustrative purposes. In the illustratedembodiment, the pump includes a first pump 1902 fluidly coupled betweenthe first reservoir 1672 and the first injector needle 1756, and asecond pump 1904 fluidly coupled between the second reservoir 1674 andthe second injector needle 1758.

In some embodiments, to initiate a rinse and/or priming operation, thecartridge support 1612 is moved to the outside position illustrated inFIG. 13B, as depicted by the horizontal arrow. If the luminescencecartridge 1628 was already loaded on the cartridge support 1612, theluminescence cartridge 1628 is moved together with the cartridge support1612 to the outside position. On the other hand, if the luminescencecartridge 1628 was not already loaded on the cartridge support 1612, theluminescence cartridge 1628 is loaded on the cartridge support 1612after the cartridge support 1612 has been moved to the outside position.Once the cartridge support 1612 and luminescence cartridge 1628 are atthe outside position, the reservoir support 1676 and reagent reservoirs1672 and 1674 supported thereon may be moved to an outside position asalso illustrated in FIG. 13B, by sliding the reservoir support 1676 asdepicted by the vertical arrow. For this purpose, the reservoir support1676 may be movably mounted to the cartridge housing 1632 by linearguides or tracks, etc., as appreciated by persons skilled in the art. Atthe outside position, the reagent reservoirs 1672 and 1674 may bereplaced as needed.

Additionally, after the cartridge support 1612 and luminescencecartridge 1628 have been moved to the outside position, an externalrinsing/priming station 1910 may be mounted to the cartridge support1612 and/or luminescence cartridge 1628. The rinsing/priming station1910 may include an external liquid container (or tank) 1914. In someembodiments, the rinsing/priming station 1910 may also include anexternal reservoir support 1916 for holding one or more rinsing/primingreservoirs 1922 and 1924 (e.g., bottles).

FIG. 14 is a perspective view of an example of the externalrinsing/priming station 1910 according to some embodiments. FIG. 15 is aperspective view of the external rinsing/priming station 1910 as mountedto the cartridge support 1612 and/or luminescence cartridge 1628. Therinsing/priming station 1910 may include one or more mounting featuresas needed for mounting the rinsing/priming station 1910 to the cartridgesupport 1612 and/or luminescence cartridge 1628. For example, therinsing/priming station 1910 may include a mounting feature 2028configured for engaging the cartridge housing 1632. In the illustratedembodiment, the rinsing/priming station 1910 is configured such that theexternal liquid container 1914 extends below the cartridge support 1612when in the mounting position. The external liquid container 1914includes a port 2032 that is aligned with the injector assembly 1636when in the mounting position. Thus, after mounting the rinsing/primingstation 1910, the injector assembly 1636 may be lowered into or throughthe port 2032 such that the injector assembly 1636 fluidly communicateswith the interior of the external liquid container 1914.

A rinsing operation may be implemented while the luminescence cartridge1628 is in the mounting position and the injector assembly 1636 isinserted in the port 2032. First, the reagent reservoirs 1672 and 1674may be filled with an appropriate rinse solution. Alternatively, thefluid lines from the pumps 1902 and 1904 may be disconnected from thereagent reservoirs 1672 and 1674 and reconnected to one or more rinsingreservoirs 1922 and 1924 provided at the external reservoir support1916. Alternatively, the rinsing reservoirs 1922 and 1924 may be placedin the position of the reagent reservoirs 1672 and 1674 in preparationfor rinsing, instead of utilizing (or providing) the external reservoirsupport 1916. In all such cases, the pumps 1902 and 1904 may then beoperated to flow the rinse solution through the pumps 1902 and 1904,injector needles 1756 and 1758, and associated fluid lines, and into theexternal liquid container 1914 via the port 2032.

Likewise, a priming operation may be implemented while the luminescencecartridge 1628 is in the mounting position and the injector assembly1636 is inserted in the port 2032. First, the reagent reservoirs 1672and 1674 may be filled with the respective first reagents and secondreagents. The pumps 1902 and 1904 may then be operated to flow therespective first reagents and second reagents through the pumps 1902 and1904, injector needles 1756 and 1758, and associated fluid lines, withthe excess reagent solution captured in the external liquid container1914 via the port 2032.

Referring back to FIG. 10, apart from the rinsing and priming of thesystem, a liquid/air mixture may be dispensed during the normaldispensing operation of the luminescence cartridge 1628, e.g., duringthe dispensing of reagent or other fluid from one of the injectorneedles 1756 and 1758 onto the sample 1616. If the injector system isrunning out of liquid, it may dispense a liquid/air mixture andconsequently generate bubbles. In some embodiments, this problem may beaddressed by providing capacitive bubble sensors 1692 and 1694operatively communicating with the fluid lines 1682 and 1684,respectively, between the pump 1678 and the injector needles 1756 and1758. As depicted by dashed lines, the capacitive bubble sensors 1692and 1694 may communicate with the electronics 1688 of the luminescencecartridge 1628.

FIG. 16 is a schematic view of an example of a capacitive bubble sensor2200 in operative communication with one of the injector needles 1756and associated fluid line 1682 (shown in cross-section) according tosome embodiments. The capacitive bubble sensor 2200 may include a signalgenerator 2204 electrically communicating with the injector needle 1756,such as by tapping an electrical lead from the signal generator 2204 toan electrically conductive portion of the injector needle 1756 that isexposed to the fluid flow. The capacitive bubble sensor 2200 may alsoinclude a detector 2208 (e.g., a metal sleeve, or a metal tubingconnector that connects two tubes, etc.) that at least partiallysurrounds a portion of the fluid line 1682. By this configuration, theelectrically conductive portion of the injector needle 1756 (contactingthe electrolytic fluid flowing through the injector needle 1756) formsone side of the capacitor, the detector 2208 forms the other side of thecapacitor, and the wall of the fluid line 1682 serves as the dielectricbetween the two sides of the capacitor. Electrical leads connect thesignal generator 2204 and the detector 2208 to the electronics 1688(FIG. 10) of the luminescence cartridge 1628. An additional electricallead from the electronics 1688 may provide a source of voltage to thesignal generator 2204. In operation, the signal generator 2204 maytransmit a pulse to the injector needle 1756, such as between ground anda low voltage value (e.g., 2 V). The electronics 1688 are configured tocontinuously measure the capacitance between the two sides of thecapacitor formed by the foregoing arrangement, and to detect when achange in capacitance correlates to the presence of a bubble, asappreciated by persons skilled in the art. The electronics 1688 may beconfigured to shut down the liquid dispensing operation when a bubble isdetected, thereby preventing contamination of the internal optics of thesample analyzing apparatus 1600 (FIG. 10). For example, the electronics1688 may transmit an output (control) signal to the pump 1678 (FIG. 10),or to a pump controller controlling the pump 1678, that ceases operationof the pump 1678.

Another problem that may arise during the course of operating theinjector system is the generation of unwanted microdroplets that mayalso contaminate the optics of the sample analyzing apparatus 1600. Suchmicrodroplets may be accelerated by electrostatic forces developed indielectric materials utilized in the sample analyzing apparatus 1600.Such dielectric materials may include, for example, the sample support1618, certain pump components contacting the liquid, and one or moreportions of the injector needles 1756 and 1758 (e.g., lining, coatedtip, etc.). This problem may be addressed by grounding dielectriccomponents where practicable to minimize or eliminate electrostaticforces.

For example, in the embodiment illustrated in FIG. 16, the injectorneedle 1756 may include an electrically conductive (e.g., metal) wall2232, the inside surface of which is lined with a non-metal (anddielectric) coating (or layer) 2234 such as polytetrafluoroethylene(PTFE) to render the inside surface inert to the liquid. Theelectrically conductive wall 2232 may be placed in communication with anelectrical ground. In embodiments providing the capacitive bubble sensor2200, the electrical connection between the electrically conductive wall2232 and the signal generator 2204 (which is grounded) may be utilizedfor this purpose. At this electrical connection, a portion of thenon-metal coating 2234 may be removed (may be absent) to expose theliquid to the electrically conductive wall 2232 at this location. Thatis, the non-metal coating 2234 may include an uncovered region 2236 notcovered by the non-metal coating at this location.

Alternatively, in another embodiment the coating 2234 may have anon-metal composition that renders the coating 2234 electricallyconductive instead of exhibiting dielectric behavior. For example, thecomposition of the coating 2234 may be an organic polymer havingsufficient carbon to be electrically conductive, such as a conductivepolymer or a normally dielectric formulation such as PTFE that ismodified to have a higher carbon content. In such embodiments, eitherthe wall 2232 or the coating 2234 may be grounded.

As another alternative, at least a portion of the injector needle 1756or a coating 2234 thereon may be composed of an antistatic plastic,which may be placed in communication with an electrical ground.

In addition to or as an alternative to one or more of the foregoingembodiments, the fluid line 1682 may be connected to electrical groundas illustrated. Additionally, the fluid line 1682 may be composed of orcoated with an antistatic plastic.

Referring back to FIG. 10, as noted elsewhere the sample support 1618 isoften a multi-well plate providing a two-dimensional array of individualwells 1620. Such multi-well plates are available in a variety ofstandardized formats as to overall dimensions, number of rows andcolumns, etc. Thus, any given format is associated with a predefined setof well positions. In the operation of the sample analyzing apparatus1600, the user may provide information accurately identifying the formatbeing utilized to the sample analyzing apparatus 1600, such as byinputting data into or programming the sample analyzing apparatus 1600.This ensures coordination and alignment of moving parts relative to eachother, such as between the injector assembly 1636 and the sample support1618. However, it is possible that the sample analyzing apparatus 1600may be set up to handle a sample support 1618 of a particular type offormat, but the user actually loads a different format onto the samplecarrier 1614. For example, the user may load a differently sized samplesupport, or a sample support providing an incomplete array of wells,i.e., the user may utilize incomplete “strip plates” as appreciated bypersons skilled in the art. In such cases, there is a risk that theinjector assembly 1636 may dispense liquid directly onto opticscomponents, such as optics components below or proximate to the samplecarrier 1614.

In some embodiments, this problem may be addressed by providing a wellsensor 1698 in the apparatus housing. The well sensor 1698 may beconfigured for detecting the presence of individual wells 1620 of thesample support 1618 according to a predefined set of well positionsprogrammed into the sample analyzing apparatus 1600. For this purpose,the well sensor 1698 may be an optical sensor and thus may include alight source for emitting a light beam toward the sample support 1618,and a well sensor detector (i.e., a light detector) for receiving alight beam from the sample support 1618, as schematically depicted bydashed arrows. The light source and well sensor detector may both belocated on the same side of the sample support 1618 (and sample carrier1614), and thus may be contained in the same housing (as illustrated).Alternatively, light source and well sensor detector may be located onopposite sides (e.g., top and bottom) of the sample support 1618 (andsample carrier 1614). Thus, depending on design, the optical signalutilized to interrogate the sample support 1618 may be transmittedthrough the wells 1620 or reflected from the surface of the wells 1620.In either case, the well sensor detector is optically aligned with thelight source so as to receive light emitted from the sample support 1618in response to light from the light source incident on the samplesupport 1618. Generally, as appreciated by persons skilled in the art,the well sensor 1698 may be configured for distinguishing the presenceor absence of wells 1620 according to a variety of measuring principlessuch as, for example, measuring the attenuation of the light received bythe well sensor detector, sensing a change in refractive index of thesurface of the sample support 1618, etc. As an example of operation,after the sample support 1618 has been mounted on the sample carrier1614, the sample carrier 1614 is moved in an indexed manner relative tothe well sensor 1698 to check for the presence of a complete array ofwells 1620 and verify that the number and positions of the wells 1620match with the predefined set of well positions. If the well sensor 1698determines that one or more wells are missing from the desired format,the well sensor 1698 may cause the analyzing apparatus 1600 to ceaseoperations, such as by transmitting a control signal to the electronics1688.

Also in the operation of the sample analyzing apparatus 1600, the usermay provide information to the sample analyzing apparatus 1600accurately indicating the amount of reagent or other liquid to bedispensed by the injector needle(s) 1756 and 1758 into each well 1620 ofthe sample support 1618. The dispensing of precise aliquots may beimportant for a given type of experiment, and also prevents overfillingof the wells 1620, which may cause spillage and contamination of opticscomponents of the sample analyzing apparatus 1600. It is possible thatthe user may enter incorrect information as to how much liquid todispense, or as to how much liquid is already contained in the wells1620 prior to a subsequent dispensing step, in either case leading tooverfilling. In some embodiments, this problem may be addressed byproviding a liquid sensor positioned to sense an overfilling event. Insome embodiments, the liquid sensor may be integrated with the injectorassembly 1636, exploiting the fact that the distal tip of the injectorassembly 1636 may be operated in close proximity to the upper surface ofthe sample support 1618.

As examples, FIG. 17 is a schematic cross-sectional view of the injectorassembly 1636 and electronics 1688 of the luminescence cartridge 1628.For clarity, the light guide 1754 (FIG. 11) is not shown. In variousembodiments, one or more of the injector needles 1756 and 1758 provided,and/or the injector housing 1646, may be utilized as part of the liquidsensor by placing electrically conductive portions of these componentsin communication with the electronics 1688 using wires as schematicallydepicted by dashed lines. In this manner, excess liquid on the top ofthe sample support 1618 may enter the distal tip of the injector housing1646 and complete an electrical circuit between two of these components,whereby the presence of such liquid may be detected by the electronics1688 by detecting an electrical current between the two components. Inresponse, the electronics 1688 may cause the sample analysis system 1600to cease operations.

In one embodiment, the liquid sensor may include a first wireelectrically coupled to one of the injector needles 1756 and 1758 at orproximate to the needle outlet, and a second wire electrically coupledto the injector housing 1646 at or proximate to the distal housing end.In this embodiment, an electrical current between the injector needle1756 or 1758 and the injector housing 1646 indicates the presence ofliquid.

In another embodiment, the liquid sensor may include a first wireelectrically coupled to the first injector needle 1756 at or proximateto the needle outlet, and a second wire electrically coupled to thesecond injector needle 1758 at or proximate to the needle outlet. Inthis embodiment, an electrical current between the injector needles 1756and 1758 indicates the presence of liquid.

In another embodiment, the liquid sensor may include a first wireelectrically coupled to one of the injector needles 1756 and 1758 (or tothe injector housing 1646) at or proximate to the needle outlet, and anelectrical contact 2304 positioned at or proximate to the needle outletwith a second wire electrically coupled thereto. In this embodiment, anelectrical current between the injector needle 1756 or 1758 (or theinjector housing 1646) and the electrical contact 2304 indicates thepresence of liquid.

FIG. 20 is a schematic cross-sectional view of another example of aninjector or injector/reader assembly 1636 and electronics 1688 of aluminescence cartridge. In this embodiment, one of the components of theliquid sensor may be an electrically conductive tube or ring 2306surrounding the light guide 1754, thus residing between the light guide1754 and the injector needles 1756 and 1758, and electrically coupled tothe electronics 1688 via a wire 2308. The tube or ring 2306 may operatein conjunction with one of the injector needles 1756 and 1758, theinjector housing 1646, or the electrical contact 2304 as described above(see FIG. 17) to form the liquid sensor.

Another problem occurs when the sample analyzing apparatus 1600 is setup to handle a sample support 1618 of a particular type of format, butthe user actually loads onto the sample carrier 1614 a sample supporthaving a plate height that is different from what has been programmedinto the sample analyzing apparatus 1600. If the plate height is lowerthan the expected height, then the distance or gap between the tip(s) ofthe injector needle(s) 1756 and 1758 and the wells 1620 of the samplesupport 1618 (i.e., the upper surface, or top, of the sample support1618) will be too large at the normal dispensing position of theinjector assembly 1636. This creates the risk of liquid dispensed fromthe injector assembly 1636 contaminating wells adjacent to the targetwell and/or contaminating optics proximate to or below the samplesupport 1618. In some embodiments, this problem may be addressed byproviding a gap sensor positioned and configured for measuring the gapbetween the tip of the injector assembly 1636 and the top of the samplesupport 1618.

As an example, FIG. 18 is an elevation view of the sample analyzingapparatus 1600 in which a gap sensor 2404 is provided in the apparatushousing below the luminescence cartridge 1628. The gap sensor 2404includes a light source 2406 and a gap sensor detector 2408 (i.e., alight detector) optically aligned with the light source 2406. The lightsource 2406 and the gap sensor detector 2408 may be positioned onopposite sides of the sample support 1618, with the optical axis betweenthe light source 2406 and the gap sensor detector 2408 being oriented inthe transverse (horizontal) plane. By this configuration and asillustrated, the light source 2406 is configured for emitting a lightbeam through the gap and incident on the tip and the sample support. Inthis manner, the gap may be measured, such as by measuring thedifference in elevation between the tip of the injector assembly 1636and the top of the sample support 1618, or by measuring the elevation ofthe top of the sample support 1618 relative to a known reference datum.If the measured gap exceeds some threshold value, the gap sensor 2404may be configured to output a control signal that causes the sampleanalysis system 1600 to cease operations. In some embodiments, the gapsensor 2404 may also be utilized to measure the elevation of the tip ofthe injector assembly 1636 relative to a known reference datum, for thepurpose of verifying that the injector assembly 1636 has been extendedto a desired operating position in close proximity to the sample support1618.

Another problem that may occur unexpectedly or during the normal courseoperation of the injector system is that a fluid line (e.g., tubing) orfluidic fitting may malfunction and cause liquid to leak into theinterior of the cartridge housing 1632. Such an event may potentiallycontaminate one or more components of the luminescence cartridge 1628.In some embodiments, this problem may be addressed by providing a liquidsensor (or leak sensor) configured for detecting liquid accumulating ina bottom section of the cartridge housing 1632.

As an example, FIG. 19 is an elevation view of the luminescencecartridge 1628 in which a liquid sensor 2504 is provided in thecartridge housing 1632. The cartridge housing 1632 may be constructed ina liquid-tight manner and sized to potentially hold the equivalent of atleast one reagent reservoir 1672 or 1674 (FIG. 10). The liquid sensor2504 may be positioned at or near a bottom wall of the cartridge housing1632. In some embodiments, the liquid sensor 2504 may be a capacitivesensor positioned at the bottom wall and communicating with theelectronics 1688 via wires. The conductive components of the liquidsensor 2504 may be encapsulated between a substrate such as a PCB and athin insulating layer to protect the conductive components from exposureto liquid. The liquid sensor 2504 may be sensitive to liquid contactingthe liquid sensor 2504, as manifested by a change in capacitance. Theelectronics 1688 may be configured for detecting a change in capacitanceresulting from the presence of leaking liquid on the capacitive sensor,and in response cause the sample analysis system 1600 to ceaseoperations.

According to another embodiment of the present invention, a method foranalyzing a target in a sample is provided. According to thisembodiment, a cartridge system having a cartridge support and one ormore cartridges that are removably engaged with a cartridge support isselected. The cartridges may be one or more of the cartridges describedherein. Then, a first cartridge contained within the cartridge system isselected. A second cartridge, i.e., a new or replacement cartridge, notcontained within the cartridge system is then selected. The firstcartridge is then replaced with the second cartridge and a target in asample is analyzed with the second cartridge. In some embodiments, thefirst cartridge may be removed from the apparatus and replaced with thesecond cartridge without the use of mechanical tools, and after thefirst cartridge is replaced with the second cartridge, the system isinstructed, with apparatus-readable instructions, with information foranalyzing the target in the sample.

According to other embodiments, the sample analyzing apparatus is anoptical reader system that does not utilize cartridges, i.e., the sampleanalyzing apparatus is a non-cartridge based sample analyzing apparatus.The configuration of the sample analyzing apparatus may be dedicated forluminescence-based measurement techniques. Alternatively, the sampleanalyzing apparatus may be reconfigurable for implementing differenttypes of measurement techniques (e.g., luminescence, absorbance,fluorescence, etc.). For luminescence measurement entailing the use of aliquid injector system, one or more components of the liquid injectorsystem may be removably mounted in the apparatus housing of the sampleanalyzing apparatus. For this purpose, a user may access the interior ofthe apparatus housing via a top panel (lid) or other panel or door ofthe apparatus housing. In such embodiments, instead of providing acartridge support, the sample analyzing apparatus may include mountingfeatures in the apparatus housing for mounting components of theinjector system, including an injector assembly (which may be configuredas described above, with or without an integral light guide), one ormore pumps, liquid lines, and reagent reservoirs. The sample analyzingapparatus may also include a movable sample carrier for supporting oneor more samples (or for supporting a sample support that holds orcontains such samples, such as a multi-well plate) as described above.The sample analyzing apparatus may also include one or more opticaldetectors, as well as electronics communicating with various bubble andliquid sensors, as described above. Generally, the structure andoperation of any or all of the foregoing components of the sampleanalyzing apparatus may be consistent with those described above inconjunction with other embodiments disclosed herein. For example, FIGS.10 to 18 may be considered as generally representative of such a sampleanalyzing apparatus, with the understanding various components would bepositioned directly in the apparatus housing instead of in a cartridge.In such embodiments, the injector assembly may be mounted in a fixedposition and the sample carrier may be moved to properly position thesample relative to the injector assembly. Thus, a driver for moving theinjector assembly as described above need not be provided. Inembodiments where the injector assembly does not include a light guide,a bottom read head as described above may be utilized.

In embodiments of the non-cartridge based sample analyzing apparatus,rinsing and priming may again be performed outside of the apparatushousing, by removing the injector assembly and other components of theinjector system as needed to avoid dispensing liquid or liquid/airmixtures onto sensitive components in the interior of the apparatushousing. After the injector assembly has been moved to an outsideposition, an external rinsing/priming station including an externalliquid container may be utilized in a manner analogous to thecartridge-based embodiments described above. The non-cartridge basedsample analyzing apparatus may also include one or more of the sensorsand liquid dispensing control features described above in conjunctionwith FIGS. 10-18, such as the capacitive bubble sensors 1692, 1694, and2200, the electrical grounding features described above in conjunctionwith FIG. 16, the well sensor 1698, the use of the injector assembly asa liquid sensor to prevent overfilling of sample wells, and the gapsensor 2404.

Exemplary Embodiments

Exemplary embodiments provided in accordance with the presentlydisclosed subject matter include, but are not limited to, the following:

1. A sample analyzing apparatus, comprising: an apparatus housing; asample carrier disposed in the apparatus housing and configured forsupporting a sample; a reagent reservoir; a pump communicating with thereagent reservoir; an injector assembly disposed in the apparatushousing and comprising an injector housing and an injector needleextending through the injector housing and configured for communicatingwith the reagent reservoir via the pump; and a luminescence detectorpositioned in the apparatus housing to receive optical signals from thesample.

2. The sample analyzing apparatus of embodiment 1, wherein the samplecarrier is movable to align the injector assembly with a samplecontained on the sample carrier.

3. The sample analyzing apparatus of embodiment 1, comprising aluminescence cartridge removably mounted at the sample analyzingapparatus, the luminescence cartridge comprising a cartridge housingcomprising a cartridge housing opening, and a driver disposed in thecartridge housing, wherein the reservoir support and the pump aredisposed in the cartridge housing, and the injector assembly is at leastpartially disposed in the cartridge housing and is movable by the driverthrough the cartridge housing opening and alternately toward and awayfrom the sample carrier.

4. The sample analyzing apparatus of embodiment 3, wherein theluminescence cartridge comprises an electrical connector mounted at thecartridge housing and in signal communication with the driver and thepump, the electrical connector configured for removable coupling to thesample analyzing apparatus to receive power from and transmit signals toor from the sample analyzing apparatus.

5. The sample analyzing apparatus of embodiment 4, comprising a featuredisposed in the apparatus housing and communicating with the electricalconnector when the luminescence cartridge is removably mounted at thesample analyzing apparatus, the feature selected from the groupconsisting of: a power source; signal processing circuitry configuredfor receiving detection signals from the luminescence detector; a drivecontroller configured for transmitting control signals to the driver; apump controller configured for transmitting control signals to the pump;and a combination of two or more of the foregoing.

6. The sample analyzing apparatus of embodiment 3, wherein the injectorassembly comprises a light guide extending through the injector housingand configured for communicating with the luminescence detector.

7. The sample analyzing apparatus of embodiment 6, wherein theluminescence detector is disposed in the cartridge housing.

8. The sample analyzing apparatus of embodiment 6, wherein the cartridgehousing comprises an optical output port, and the light guide is coupledto or extends through the optical output port.

9. The sample analyzing apparatus of embodiment 6, wherein the injectorhousing comprises a distal housing end, the injector needle comprises aneedle outlet at the distal housing end, and the injector assemblycomprises a liquid sensor configured for detecting liquid at the housingend, the liquid sensor comprising an electrically conductive tubesurrounding the light guide and configured for communicating withelectronics configured for detecting an electrical current between theelectrically conductive tube and the injector needle or between theelectrically conductive tube and the injector housing.

10. The sample analyzing apparatus of embodiment 3, wherein thereservoir support is movable between an inside reservoir supportposition at which the reservoir support is positioned entirely in thecartridge housing and an outside reservoir support position at which thereservoir support is positioned at least partially outside the cartridgehousing.

11. The sample analyzing apparatus of embodiment 3, comprising a liquidsensor configured for detecting liquid accumulating in a bottom sectionof the cartridge housing.

12. The sample analyzing apparatus of embodiment 11, wherein thecartridge housing comprises a bottom wall through which the cartridgehousing opening is formed, and the liquid sensor comprises a capacitivesensor positioned at the bottom wall and configured for communicatingwith electronics configured for detecting a signal from the capacitivesensor indicative of the presence of liquid on the capacitive sensor.

13. The sample analyzing apparatus of embodiment 3, comprising acartridge support configured for receiving the luminescence cartridgesuch that the luminescence cartridge is removably mounted thereto, thecartridge support movable between an inside cartridge support positionat which the cartridge support is positioned entirely in the apparatushousing and an outside cartridge support position at which the cartridgesupport is positioned at least partially outside the apparatus housing.

14. The sample analyzing apparatus of embodiment 13, wherein thecartridge support is movable to align the injector assembly with asample contained on the sample carrier.

15. The sample analyzing apparatus of embodiment 13, wherein thecartridge support comprises a plurality of cartridge positionsconfigured for receiving the luminescence cartridge and one or moreother removable cartridges concurrently.

16. The sample analyzing apparatus of embodiment 13, wherein theapparatus housing comprises an outer wall having an apparatus housingopening through which the cartridge support is movable along a firstdirection between the inside cartridge support position and the outsidecartridge support position.

17. The sample analyzing apparatus of embodiment 16, wherein thereservoir support is movable along a second direction perpendicular tothe first direction, between an inside reservoir support position atwhich the reservoir support is positioned entirely in the cartridgehousing and an outside reservoir support position at which the reservoirsupport is positioned at least partially outside the cartridge housing.

18. The sample analyzing apparatus of embodiment 17, wherein thereservoir support is movable to the outside reservoir support positionwhen the cartridge support is at the outside cartridge support position,and at the outside reservoir support position the reservoir support isin an overlapping relation with the outer wall such that the reservoirsupport prevents the cartridge support from being moved to the insidecartridge support position.

19. The sample analyzing apparatus of embodiment 13, comprising anexternal liquid container removably mountable to at least one of theluminescence cartridge and the cartridge support while the cartridgesupport is at the outside cartridge support position, the externalliquid container comprising a port configured for receiving the injectorassembly, wherein the injector assembly is movable by the driveralternately into and out from the port.

20. The sample analyzing apparatus of embodiment 19, wherein theapparatus housing comprises an outer wall having an apparatus housingopening through which the cartridge support is movable between theinside cartridge support position and the outside cartridge supportposition, and the external liquid container is configured foroverlapping with the outer wall when the external liquid container ismounted to the luminescence cartridge or the cartridge support, suchthat the external liquid container prevents the cartridge support frombeing moved to the inside cartridge support position.

21. The sample analyzing apparatus of embodiment 1, comprising a wellsensor configured for detecting the presence of individual wells of asample support disposed on the sample carrier according to a predefinedset of well positions, wherein the sample carrier is movable to alignthe sample support sensor with each well position.

22. The sample analyzing apparatus of embodiment 21, wherein the wellsensor comprises a light source and a well sensor detector aligned withthe light source, and wherein either or both of the light source and thewell sensor are positioned above or below the sample carrier.

23. The sample analyzing apparatus of embodiment 1, comprising a gapsensor configured for measuring a gap between a tip of the injectorassembly and a top of a sample support disposed on the sample carrier.

24. The sample analyzing apparatus of embodiment 23, wherein the gapsensor comprises a light source and a gap sensor detector aligned withthe light source, and the light source configured for emitting a lightbeam through the gap and incident on the tip and the sample support.

25. The sample analyzing apparatus of embodiment 1, wherein the injectorneedle is a first injector needle configured for communicating with afirst reagent reservoir, and the injector assembly further comprises asecond injector needle extending through the injector housing andconfigured for communicating with a second reagent reservoir supportedby the reservoir support via the pump.

26. The sample analyzing apparatus of embodiment 1, wherein the injectorneedle has a configuration selected from the group consisting of: theinjector needle is composed of an electrically conductive material andcommunicates with an electrical ground; the injector needle is composedof an electrically conductive material and communicates with anelectrical ground, and the injector needle comprises an inside surfaceand a non-metallic coating on the inside surface, wherein the insidesurface comprises an uncovered region not covered by the non-metalcoating such that liquid flowing through the injector needle is exposedto the uncovered region; the injector needle is composed of anelectrically conductive material and communicates with an electricalground, and the injector needle comprises an inside surface and anon-metallic, electrically conductive coating on the inside surface; atleast a portion of the injector needle is composed of or coated with anantistatic plastic and communicates with an electrical ground, whereinliquid flowing through the injector needle is exposed to the antistaticplastic; and the sample analyzing apparatus comprises a plastic tubefluidly coupled between the pump and the injector needle, the plastictube is composed of or coated with an antistatic plastic andcommunicating with an electrical ground, wherein liquid flowing throughthe injector needle is exposed to the antistatic plastic.

27. The sample analyzing apparatus of embodiment 1, comprising a tubefluidly coupled between the pump and the injector needle, and a bubblesensor configured for detecting a bubble in the tube.

28. The sample analyzing apparatus of embodiment 1, wherein the injectorhousing comprises a distal housing end, the injector needle comprises aneedle outlet at the distal housing end, and the injector assemblycomprises a liquid sensor disposed in the injector housing andconfigured for detecting liquid at the housing end.

29. The sample analyzing apparatus of embodiment 1, wherein the injectorhousing comprises a distal housing end, the injector needle comprises aneedle outlet at the distal housing end, and the injector assemblycomprises a liquid sensor disposed in the injector housing andconfigured for detecting liquid at the housing end.

30. The sample analyzing apparatus of embodiment 29, wherein the liquidsensor has a configuration selected from the group consisting of: theliquid sensor comprises a first wire electrically coupled to theinjector needle at or proximate to the needle outlet, and a second wireelectrically coupled to the injector housing at or proximate to thedistal housing end, wherein the first wire and the second wire areconfigured for communicating with electronics configured for detectingan electrical current between the injector needle and the injectorhousing; the liquid sensor comprises an electrical contact positioned atthe same or substantially the same elevation as the needle outlet, afirst wire electrically coupled to the electrical contact, and a secondwire electrically coupled to the injector needle at or proximate to theneedle outlet or to the injector housing at or proximate to the distalhousing end, wherein the first wire and the second wire are configuredfor communicating with electronics configured for detecting anelectrical current between the electrical contact and the injectorneedle or between the electrical contact and the injector housing;wherein the injector needle is a first injector needle, the needleoutlet is a first needle outlet, and the injector assembly furthercomprises a second injector needle extending through the injectorhousing comprising a second needle outlet, and the liquid sensorcomprises a first wire electrically coupled to the first injector needleat or proximate to the first needle outlet, and a second wireelectrically coupled to the second injector needle at or proximate tothe second needle outlet, wherein the first wire and the second wire areconfigured for communicating with electronics configured for detectingan electrical current between the first injector needle and the secondinjector needle; the liquid sensor comprises an electrically conductivetube configured for communicating with electronics configured fordetecting an electrical current between the electrically conductive tubeand the injector needle or between the electrically conductive tube andthe injector housing.

31. A luminescence cartridge for use in a sample analyzing apparatus,the luminescence cartridge comprising: a cartridge housing comprising acartridge housing opening; a reservoir support disposed in the cartridgehousing and configured for supporting a reagent reservoir; a pumpcommunicating with the reagent reservoir; a driver disposed in thecartridge housing; an injector/reader assembly at least partiallydisposed in the cartridge housing and comprising an injector/readerhousing, an injector needle extending through the injector/readerhousing and configured for communicating with a reagent reservoirsupported by the reservoir support via the pump, and a light guideextending through the injector/reader housing and configured forcommunicating with a luminescence detector, wherein the injector/readerassembly is movable by the driver through the cartridge housing openingand alternately toward and away from the cartridge housing; and anelectrical connector mounted at the cartridge housing and in signalcommunication with the driver and the pump, the electrical connectorconfigured for removable coupling to the sample analyzing apparatus toreceive power from and transmit signals to or from the sample analyzingapparatus.

32. A sample analyzing apparatus, comprising: the luminescence cartridgeof embodiment 31; an apparatus housing; a sample carrier disposed in theapparatus housing; and a cartridge support configured for receiving theluminescence cartridge such that the luminescence cartridge is removablymounted thereto, the cartridge support movable between an insidecartridge support position at which the cartridge support is positionedentirely in the apparatus housing and an outside cartridge supportposition at which the cartridge support is positioned at least partiallyoutside the apparatus housing, wherein: the injector/reader assembly ismovable by the driver alternately toward and away from the samplecarrier; and at least one of the sample carrier and the cartridgesupport is movable to align the injector/reader assembly with a samplecontained on the sample carrier.

33. The sample analyzing apparatus of embodiment 32, comprising anexternal liquid container removably mountable to at least one of theluminescence cartridge and the cartridge support while the cartridgesupport is at the outside cartridge support position, the externalliquid container comprising a port configured for receiving theinjector/reader assembly, wherein the injector/reader assembly ismovable by the driver alternately into and out from the port.

34. A method for analyzing a sample, the method comprising: positioningan injector assembly in alignment with and at a desired distance from asample in a sample analyzing apparatus, the injector assembly comprisingan injector housing and an injector needle extending through theinjector housing; injecting a reagent from the injector needle to thesample by operating the pump to establish a flow of the reagent from areagent reservoir to the injector needle; and detecting luminescentlight emitted from the sample at a luminescence detector.

35. The method of embodiment 34, comprising moving the injector assemblyto the desired distance from the sample by operating a driver in thesample analyzing apparatus.

36. The method of embodiment 34, wherein positioning the injectorassembly comprises moving a sample carrier on which the sample issupported.

37. The method of embodiment 34, wherein the injector needle is a firstinjector needle configured for communicating with a first reagentreservoir for injecting a first reagent, and the injector assemblyfurther comprises a second injector needle extending through theinjector housing and communicating with a second reagent reservoirsupported by the reservoir support via the pump, and further comprising:after injecting the first reagent and receiving luminescent light,injecting a second reagent from the second injector needle, andtransmitting to the luminescence detector luminescent light emitted fromthe sample in response to injecting the second reagent.

38. The method of embodiment 37, wherein the first reagent comprisesfirefly luciferase and the second reagent comprises Renilla luciferase.

39. The method of embodiment 34, comprising electrically grounding theinjector needle, or electrically grounding a tube fluidly coupledbetween the pump and the injector needle, to suppress static electricityin liquid flowing through the injector needle.

40. The method of embodiment 34, comprising removing the injectorassembly from the sample analyzing apparatus, and performing a rinsingor priming operation by flowing a liquid through the injector needlewhile the injector assembly is outside of the sample analyzingapparatus.

41. The method of embodiment 40, comprising placing an external liquidsource in fluid communication with the pump, placing an external liquidcontainer in fluid communication with the injector needle, and flowingthe liquid through the injector needle and into the external liquidcontainer by operating the pump.

42. The method of embodiment 41, wherein placing the external liquidcontainer in fluid communication with the injector needle comprisesmoving the injector assembly into a port of the external liquidcontainer.

43. The method of embodiment 34, comprising monitoring a tube fluidlycoupled between the pump and the injector needle for the presence of abubble in the tube.

44. The method of embodiment 34, wherein the sample is supported on amulti-well sample support, and comprising operating a well sensor todetermine whether the multi-well sample support is configured accordingto a predefined set of well positions.

45. The method of embodiment 34, comprising operating a liquid sensor inthe injector housing to detect for the presence of liquid in theinjector housing outside of the injector needle.

46. The method of embodiment 34, comprising operating a gap sensor tomeasure a gap between a tip of the injector assembly and a top of asample support at which the sample is supported.

47. The method of embodiment 34, wherein the sample analyzing apparatuscomprises a cartridge support, and further comprising: loading aluminescence cartridge on the cartridge support, wherein theluminescence cartridge comprises a cartridge housing comprising acartridge housing opening, the pump and the reagent reservoir aredisposed in the cartridge housing, and the injector assembly is at leastpartially disposed in the cartridge housing and extends through thecartridge housing opening; and before aligning the injector assemblywith the sample, moving the luminescence cartridge into an apparatushousing of the apparatus by operating the cartridge support.

48. The method of embodiment 47, comprising moving the injector assemblyto the desired distance from the sample by operating a driver in thecartridge housing.

49. The method of embodiment 47, wherein positioning the injectorassembly comprises moving the cartridge support, moving a sample carrieron which the sample is supported, or both of the foregoing.

50. The method of embodiment 47, comprising performing a rinsing orpriming operation by flowing a liquid through the injector needle whilethe injector assembly remains assembled in the cartridge housing andwhile the cartridge housing is at least partially outside of anapparatus housing of the sample analyzing apparatus.

51. The method of embodiment 47, comprising moving the luminescencecartridge to an outside position at which the luminescence cartridge isat least partially outside of an apparatus housing of the sampleanalyzing apparatus by operating the cartridge support, placing anexternal liquid source in fluid communication with the pump, placing anexternal liquid container in fluid communication with the injectorneedle, and flowing a liquid through the injector needle and into theexternal liquid container by operating the pump.

52. The method of embodiment 51, wherein placing the external liquidcontainer in fluid communication with the injector needle comprisesmoving the injector assembly into a port of the external liquidcontainer.

53. The method of embodiment 51, comprising, while the luminescencecartridge is at the outside position, preventing the luminescencecartridge from being moved into the apparatus housing.

54. The method of embodiment 53, wherein preventing comprises at leastone of the following: moving a reservoir support on which the reagentreservoir is supported in the cartridge housing to a position at whichthe reservoir support is in an overlapping relation with an outer wallof the apparatus housing; or mounting the external liquid container tothe luminescence cartridge or the cartridge support such that theexternal liquid container is in an overlapping relation with an outerwall of the apparatus housing.

55. The method of embodiment 47, comprising operating a liquid sensor todetect for the presence of liquid accumulating in a bottom section ofthe cartridge housing.

It will be understood that one or more of the processes, sub-processes,and process steps described herein may be performed by hardware,firmware, software, or a combination of two or more of the foregoing, onone or more electronic or digitally-controlled devices. The software mayreside in a software memory (not shown) in a suitable electronicprocessing component or system such as, for example, the systemcontroller 74 schematically depicted in FIG. 3. The software memory mayinclude an ordered listing of executable instructions for implementinglogical functions (that is, “logic” that may be implemented in digitalform such as digital circuitry or source code, or in analog form such asan analog source such as an analog electrical, sound, or video signal).The instructions may be executed within a processing module, whichincludes, for example, one or more microprocessors, general purposeprocessors, combinations of processors, digital signal processors(DSPs), or application specific integrated circuits (ASICs). Further,the schematic diagrams describe a logical division of functions havingphysical (hardware and/or software) implementations that are not limitedby architecture or the physical layout of the functions. The examples ofsystems described herein may be implemented in a variety ofconfigurations and operate as hardware/software components in a singlehardware/software unit, or in separate hardware/software units.

The executable instructions may be implemented as a computer programproduct having instructions stored therein which, when executed by aprocessing module of an electronic system (e.g., the system controller74 in FIG. 3), direct the electronic system to carry out theinstructions. The computer program product may be selectively embodiedin any non-transitory computer-readable storage medium for use by or inconnection with an instruction execution system, apparatus, or device,such as a electronic computer-based system, processor-containing system,or other system that may selectively fetch the instructions from theinstruction execution system, apparatus, or device and execute theinstructions. In the context of this disclosure, a computer-readablestorage medium is any non-transitory means that may store the programfor use by or in connection with the instruction execution system,apparatus, or device. The non-transitory computer-readable storagemedium may selectively be, for example, an electronic, magnetic,optical, electromagnetic, infrared, or semiconductor system, apparatus,or device. A non-exhaustive list of more specific examples ofnon-transitory computer readable media include: an electrical connectionhaving one or more wires (electronic); a portable computer diskette(magnetic); a random access memory (electronic); a read-only memory(electronic); an erasable programmable read only memory such as, forexample, flash memory (electronic); a compact disc memory such as, forexample, CD-ROM, CD-R, CD-RW (optical); and digital versatile discmemory, i.e., DVD (optical). Note that the non-transitorycomputer-readable storage medium may even be paper or another suitablemedium upon which the program is printed, as the program can beelectronically captured via, for instance, optical scanning of the paperor other medium, then compiled, interpreted, or otherwise processed in asuitable manner if necessary, and then stored in a computer memory ormachine memory.

It will also be understood that the term “in signal communication” asused herein means that two or more systems, devices, components,modules, or sub-modules are capable of communicating with each other viasignals that travel over some type of signal path. The signals may becommunication, power, data, or energy signals, which may communicateinformation, power, or energy from a first system, device, component,module, or sub-module to a second system, device, component, module, orsub-module along a signal path between the first and second system,device, component, module, or sub-module. The signal paths may includephysical, electrical, magnetic, electromagnetic, electrochemical,optical, wired, or wireless connections. The signal paths may alsoinclude additional systems, devices, components, modules, or sub-modulesbetween the first and second system, device, component, module, orsub-module.

More generally, terms such as “communicate” and “in . . . communicationwith” (for example, a first component “communicates with” or “is incommunication with” a second component) are used herein to indicate astructural, functional, mechanical, electrical, signal, optical,magnetic, electromagnetic, ionic or fluidic relationship between two ormore components or elements. As such, the fact that one component issaid to communicate with a second component is not intended to excludethe possibility that additional components may be present between,and/or operatively associated or engaged with, the first and secondcomponents.

It will be understood that various aspects or details of the inventionmay be changed without departing from the scope of the invention.Furthermore, the foregoing description is for the purpose ofillustration only, and not for the purpose of limitation—the inventionbeing defined by the claims.

What is claimed is:
 1. A sample analyzing apparatus, comprising: anapparatus housing; a sample carrier disposed in the apparatus housingand configured for supporting a sample; a reservoir support configuredfor supporting a reagent reservoir; a pump configured for communicatingwith the reagent reservoir; an injector assembly disposed in theapparatus housing, and comprising an injector housing and an injectorneedle extending through the injector housing and configured forcommunicating with the reagent reservoir via the pump; a driverconfigured for moving the injector assembly toward and away from thesample carrier; and a luminescence detector positioned in the apparatushousing to receive optical signals from the sample, wherein: theinjector housing comprises a distal housing end, the injector needlecomprises a needle outlet at the distal housing end, and the injectorassembly comprises a liquid sensor disposed in the injector housing andconfigured for detecting liquid at the housing end; and the injectorassembly has a configuration selected from the group consisting of: theliquid sensor comprises a first wire electrically coupled to theinjector needle at or proximate to the needle outlet, and a second wireelectrically coupled to the injector housing at or proximate to thedistal housing end, wherein the first wire and the second wire areconfigured for communicating with electronics configured for detectingan electrical current between the injector needle and the injectorhousing; the liquid sensor comprises an electrical contact positioned atthe same or substantially the same elevation as the needle outlet, afirst wire electrically coupled to the electrical contact, and a secondwire electrically coupled to the injector needle at or proximate to theneedle outlet or to the injector housing at or proximate to the distalhousing end, wherein the first wire and the second wire are configuredfor communicating with electronics configured for detecting anelectrical current between the electrical contact and the injectorneedle or between the electrical contact and the injector housing; theinjector needle is a first injector needle, the needle outlet is a firstneedle outlet, and the injector assembly further comprises a secondinjector needle extending through the injector housing comprising asecond needle outlet, and the liquid sensor comprises a first wireelectrically coupled to the first injector needle at or proximate to thefirst needle outlet, and a second wire electrically coupled to thesecond injector needle at or proximate to the second needle outlet,wherein the first wire and the second wire are configured forcommunicating with electronics configured for detecting an electricalcurrent between the first injector needle and the second injectorneedle; and the liquid sensor comprises an electrically conductive tubeconfigured for communicating with electronics configured for detectingan electrical current between the electrically conductive tube and theinjector needle or between the electrically conductive tube and theinjector housing.
 2. The sample analyzing apparatus of claim 1, whereinthe sample carrier is movable to align the injector assembly with asample contained on the sample carrier.
 3. The sample analyzingapparatus of claim 1, comprising a luminescence cartridge removablymounted at the sample analyzing apparatus, the luminescence cartridgecomprising a cartridge housing comprising a cartridge housing opening,wherein the driver, the reservoir support and the pump are disposed inthe cartridge housing, and the injector assembly is at least partiallydisposed in the cartridge housing and is movable by the driver throughthe cartridge housing opening and alternately toward and away from thesample carrier.
 4. The sample analyzing apparatus of claim 3, whereinthe luminescence cartridge comprises an electrical connector mounted atthe cartridge housing and in signal communication with the driver andthe pump, the electrical connector configured for removable coupling tothe sample analyzing apparatus to receive power from and transmitsignals to or from the sample analyzing apparatus.
 5. The sampleanalyzing apparatus of claim 4, comprising a feature disposed in theapparatus housing and communicating with the electrical connector whenthe luminescence cartridge is removably mounted at the sample analyzingapparatus, the feature selected from the group consisting of: a powersource; signal processing circuitry configured for receiving detectionsignals from the luminescence detector; a drive controller configuredfor transmitting control signals to the driver; a pump controllerconfigured for transmitting control signals to the pump; and acombination of two or more of the foregoing.
 6. The sample analyzingapparatus of claim 3, wherein the luminescence detector is disposed inthe cartridge housing.
 7. The sample analyzing apparatus of claim 3,wherein the injector assembly comprises a light guide extending throughthe injector housing and configured for communicating with theluminescence detector, the cartridge housing comprises an optical outputport, and the light guide is coupled to or extends through the opticaloutput port.
 8. The sample analyzing apparatus of claim 3, wherein thereservoir support is movable between an inside reservoir supportposition at which the reservoir support is positioned entirely in thecartridge housing and an outside reservoir support position at which thereservoir support is positioned at least partially outside the cartridgehousing.
 9. The sample analyzing apparatus of claim 3, comprising anadditional liquid sensor configured for detecting liquid accumulating ina bottom section of the cartridge housing.
 10. The sample analyzingapparatus of claim 9, wherein the cartridge housing comprises a bottomwall through which the cartridge housing opening is formed, and theadditional liquid sensor comprises a capacitive sensor positioned at thebottom wall and configured for communicating with electronics configuredfor detecting a signal from the capacitive sensor indicative of thepresence of liquid on the capacitive sensor.
 11. The sample analyzingapparatus of claim 3, comprising a cartridge support configured forreceiving the luminescence cartridge such that the luminescencecartridge is removably mounted thereto, the cartridge support movablebetween an inside cartridge support position at which the cartridgesupport is positioned entirely in the apparatus housing and an outsidecartridge support position at which the cartridge support is positionedat least partially outside the apparatus housing.
 12. The sampleanalyzing apparatus of claim 11, wherein the cartridge support ismovable to align the injector assembly with a sample contained on thesample carrier.
 13. The sample analyzing apparatus of claim 11, whereinthe cartridge support comprises a plurality of cartridge positionsconfigured for receiving the luminescence cartridge and one or moreother removable cartridges concurrently.
 14. The sample analyzingapparatus of claim 11, wherein the apparatus housing comprises an outerwall having an apparatus housing opening through which the cartridgesupport is movable along a first direction between the inside cartridgesupport position and the outside cartridge support position.
 15. Thesample analyzing apparatus of claim 14, wherein the reservoir support ismovable along a second direction perpendicular to the first direction,between an inside reservoir support position at which the reservoirsupport is positioned entirely in the cartridge housing and an outsidereservoir support position at which the reservoir support is positionedat least partially outside the cartridge housing.
 16. The sampleanalyzing apparatus of claim 15, wherein the reservoir support ismovable to the outside reservoir support position when the cartridgesupport is at the outside cartridge support position, and at the outsidereservoir support position the reservoir support is in an overlappingrelation with the outer wall such that the reservoir support preventsthe cartridge support from being moved to the inside cartridge supportposition.
 17. The sample analyzing apparatus of claim 11, comprising anexternal liquid container removably mountable to at least one of theluminescence cartridge and the cartridge support while the cartridgesupport is at the outside cartridge support position, the externalliquid container comprising a port configured for receiving the injectorassembly, wherein the injector assembly is movable by the driveralternately into and out from the port.
 18. The sample analyzingapparatus of claim 17, wherein the apparatus housing comprises an outerwall having an apparatus housing opening through which the cartridgesupport is movable between the inside cartridge support position and theoutside cartridge support position, and the external liquid container isconfigured for overlapping with the outer wall when the external liquidcontainer is mounted to the luminescence cartridge or the cartridgesupport, such that the external liquid container prevents the cartridgesupport from being moved to the inside cartridge support position. 19.The sample analyzing apparatus of claim 1, comprising a well sensorconfigured for detecting the presence of individual wells of a samplesupport disposed on the sample carrier according to a predefined set ofwell positions, wherein the sample carrier is movable to align thesample support sensor with each well position.
 20. The sample analyzingapparatus of claim 19, wherein the well sensor comprises a light sourceand a well sensor detector aligned with the light source, and whereineither or both of the light source and the well sensor detector arepositioned above or below the sample carrier.
 21. The sample analyzingapparatus of claim 1, comprising a gap sensor configured for measuring agap between a tip of the injector assembly and a top of a sample supportdisposed on the sample carrier.
 22. The sample analyzing apparatus ofclaim 21, wherein the gap sensor comprises a light source and a gapsensor detector aligned with the light source, and the light sourceconfigured for emitting a light beam through the gap and incident on thetip and the sample support.
 23. The sample analyzing apparatus of claim1, wherein the injector needle has a configuration selected from thegroup consisting of: the injector needle is composed of an electricallyconductive material and communicates with an electrical ground; theinjector needle is composed of an electrically conductive material andcommunicates with an electrical ground, and the injector needlecomprises an inside surface and a non-metallic coating on the insidesurface, wherein the inside surface comprises an uncovered region notcovered by the non-metallic coating such that liquid flowing through theinjector needle is exposed to the uncovered region; the injector needleis composed of an electrically conductive material and communicates withan electrical ground, and the injector needle comprises an insidesurface and a non-metallic, electrically conductive coating on theinside surface; at least a portion of the injector needle is composed ofor coated with an antistatic plastic and communicates with an electricalground, wherein liquid flowing through the injector needle is exposed tothe antistatic plastic; and the sample analyzing apparatus comprises aplastic tube fluidly coupled between the pump and the injector needle,the plastic tube is composed of or coated with an antistatic plastic andcommunicating with an electrical ground, wherein liquid flowing throughthe injector needle is exposed to the antistatic plastic.
 24. The sampleanalyzing apparatus of claim 1, comprising a tube fluidly coupledbetween the pump and the injector needle, and a bubble sensor configuredfor detecting a bubble in the tube.
 25. The sample analyzing apparatusof claim 24, wherein the bubble sensor is configured for transmitting anoutput signal to the pump or a pump controller controlling the pump inresponse to detecting a bubble.
 26. The sample analyzing apparatus ofclaim 1, wherein the injector assembly comprises a light guide extendingthrough the injector housing and configured for communicating with theluminescence detector.
 27. A sample analyzing apparatus, comprising: anapparatus housing; a sample carrier disposed in the apparatus housingand configured for supporting a sample; a reservoir support configuredfor supporting a reagent reservoir; a pump configured for communicatingwith the reagent reservoir; an injector assembly disposed in theapparatus housing, and comprising: an injector housing; an injectorneedle extending through the injector housing and configured forcommunicating with the reagent reservoir via the pump; and a light guideextending through the injector housing; a driver configured for movingthe injector assembly toward and away from the sample carrier; and aluminescence detector positioned in the apparatus housing to receiveoptical signals from the sample via the light guide, wherein theinjector housing comprises a distal housing end, the injector needlecomprises a needle outlet at the distal housing end, and the injectorassembly comprises a liquid sensor configured for detecting liquid atthe housing end, the liquid sensor comprising an electrically conductivetube surrounding the light guide and configured for communicating withelectronics configured for detecting an electrical current between theelectrically conductive tube and the injector needle or between theelectrically conductive tube and the injector housing.
 28. The sampleanalyzing apparatus of claim 27, wherein the sample carrier is movableto align the injector assembly with a sample contained on the samplecarrier.
 29. The sample analyzing apparatus of claim 27, comprising aluminescence cartridge removably mounted at the sample analyzingapparatus, the luminescence cartridge comprising a cartridge housingcomprising a cartridge housing opening, wherein the driver, thereservoir support and the pump are disposed in the cartridge housing,and the injector assembly is at least partially disposed in thecartridge housing and is movable by the driver through the cartridgehousing opening and alternately toward and away from the sample carrier.